Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model
Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and meta...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Gaganashree Shivashankar [verfasserIn] Julie C. Lim [verfasserIn] Monica L. Acosta [verfasserIn] |
|---|
| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Übergeordnetes Werk: |
In: Journal of Ophthalmology - Hindawi Limited, 2009, (2023) |
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| Übergeordnetes Werk: |
year:2023 |
| Links: |
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| DOI / URN: |
10.1155/2023/7893104 |
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| Katalog-ID: |
DOAJ08864765X |
|---|
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| 520 | |a Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. | ||
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10.1155/2023/7893104 doi (DE-627)DOAJ08864765X (DE-599)DOAJd59241a3b845409c862ab59ec97a61ed DE-627 ger DE-627 rakwb eng RE1-994 Gaganashree Shivashankar verfasserin aut Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. Ophthalmology Julie C. Lim verfasserin aut Monica L. Acosta verfasserin aut In Journal of Ophthalmology Hindawi Limited, 2009 (2023) (DE-627)62318270X (DE-600)2546525-9 20900058 nnns year:2023 https://doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/article/d59241a3b845409c862ab59ec97a61ed kostenfrei http://dx.doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/toc/2090-0058 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2023 |
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10.1155/2023/7893104 doi (DE-627)DOAJ08864765X (DE-599)DOAJd59241a3b845409c862ab59ec97a61ed DE-627 ger DE-627 rakwb eng RE1-994 Gaganashree Shivashankar verfasserin aut Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. Ophthalmology Julie C. Lim verfasserin aut Monica L. Acosta verfasserin aut In Journal of Ophthalmology Hindawi Limited, 2009 (2023) (DE-627)62318270X (DE-600)2546525-9 20900058 nnns year:2023 https://doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/article/d59241a3b845409c862ab59ec97a61ed kostenfrei http://dx.doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/toc/2090-0058 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2023 |
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10.1155/2023/7893104 doi (DE-627)DOAJ08864765X (DE-599)DOAJd59241a3b845409c862ab59ec97a61ed DE-627 ger DE-627 rakwb eng RE1-994 Gaganashree Shivashankar verfasserin aut Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. Ophthalmology Julie C. Lim verfasserin aut Monica L. Acosta verfasserin aut In Journal of Ophthalmology Hindawi Limited, 2009 (2023) (DE-627)62318270X (DE-600)2546525-9 20900058 nnns year:2023 https://doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/article/d59241a3b845409c862ab59ec97a61ed kostenfrei http://dx.doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/toc/2090-0058 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2023 |
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10.1155/2023/7893104 doi (DE-627)DOAJ08864765X (DE-599)DOAJd59241a3b845409c862ab59ec97a61ed DE-627 ger DE-627 rakwb eng RE1-994 Gaganashree Shivashankar verfasserin aut Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. Ophthalmology Julie C. Lim verfasserin aut Monica L. Acosta verfasserin aut In Journal of Ophthalmology Hindawi Limited, 2009 (2023) (DE-627)62318270X (DE-600)2546525-9 20900058 nnns year:2023 https://doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/article/d59241a3b845409c862ab59ec97a61ed kostenfrei http://dx.doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/toc/2090-0058 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2023 |
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10.1155/2023/7893104 doi (DE-627)DOAJ08864765X (DE-599)DOAJd59241a3b845409c862ab59ec97a61ed DE-627 ger DE-627 rakwb eng RE1-994 Gaganashree Shivashankar verfasserin aut Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. Ophthalmology Julie C. Lim verfasserin aut Monica L. Acosta verfasserin aut In Journal of Ophthalmology Hindawi Limited, 2009 (2023) (DE-627)62318270X (DE-600)2546525-9 20900058 nnns year:2023 https://doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/article/d59241a3b845409c862ab59ec97a61ed kostenfrei http://dx.doi.org/10.1155/2023/7893104 kostenfrei https://doaj.org/toc/2090-0058 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2023 |
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Gaganashree Shivashankar |
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RE1-994 Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model |
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proinflammatory cytokines trigger the onset of retinal abnormalities and metabolic dysregulation in a hyperglycemic mouse model |
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RE1-994 |
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Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model |
| abstract |
Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. |
| abstractGer |
Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. |
| abstract_unstemmed |
Purpose. Recent evidence has shown that retinal inflammation is a key player in diabetic retinopathy (DR) pathogenesis. To further understand and validate the metabolic biomarkers of DR, we investigated the effect of intravitreal proinflammatory cytokines on the retinal structure, function, and metabolism in an in vivo hyperglycemic mouse model. Methods. C57Bl/6 mice were rendered hyperglycemic within one week of administration of a single high-dose intraperitoneal injection of streptozotocin, while control mice received vehicle injection. After confirming hyperglycemia, the mice received an intravitreal injection of either proinflammatory cytokines (TNF-α and IL-1β) or vehicle. Similarly, control mice received an intravitreal injection of either proinflammatory cytokines or vehicle. The retinal structure was evaluated using fundus imaging and optical coherence tomography, and retinal function was assessed using a focal electroretinogram (ERG), two days after cytokine injection. Retinas were collected for biochemical analysis to determine key metabolite levels and enzymatic activities. Results. Hyperglycemic mice intraocularly injected with cytokines developed visible retinal vascular damage and intravitreal and intraretinal hyper-reflective spots two days after the cytokines injection. These mice also developed a significant functional deficit with reduced a-wave and b-wave amplitudes of the ERG at high light intensities compared to control mice. Furthermore, metabolic disruption was evident in these mice, with significantly higher retinal glucose, lactate, ATP, and glutamine levels and a significant reduction in glutamate levels compared with control mice. Minimal or no metabolic changes were observed in hyperglycemic mice without intraocular cytokines or in control mice with intraocular cytokines at 2 days post hyperglycemia. Conclusions. Proinflammatory cytokines accelerated the development of vascular damage in the eyes of hyperglycemic mice. Significant changes were observed in retinal structure, function, and metabolic homeostasis. These findings support the idea that with the onset of inflammation in DR, there is a deficit in metabolism. Therefore, early intervention to prevent inflammation-induced retinal changes in diabetic patients may improve the disease outcome. |
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Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model |
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