Central Serotonergic Trophic Support of the Retina: Its Impairment in Retinitis Pigmentosa (in an Animal Model and in Clinics)

We analyzed possible molecular mechanisms of central serotonergic trophic support of the retina and pathogenesis of retinitis pigmentosa (RP) in an experimental model on rabbits and in patients diagnosed with this pathology. Grave-degree experimental RP was induced in male rabbits through i.v. admin...
Ausführliche Beschreibung

We analyzed possible molecular mechanisms of central serotonergic trophic support of the retina and pathogenesis of retinitis pigmentosa (RP) in an experimental model on rabbits and in patients diagnosed with this pathology. Grave-degree experimental RP was induced in male rabbits through i.v. administration of monoiodoacetic acid (MIAA, 26 mg/kg body mass). With application of an indirect ELISA test, the levels of heat shock protein 70 kDa (HSP70) and rhodopsin in the retina and those of natural anti-SMAP autoantibodies in blood serum of the patients were measured. Serotoninmodulating anticonsolidation protein (SMAP, [5]) and anti-SMAP antibodies were administered to the animals with RP. Significant downregulation of the ERG amplitude elicited by light flashes of different intensities (P < 0.001), downregulation of the rhodopsin content (P < 0.001), and upregulation of HSP70 content (P < 0.001) in the retina of MIAA-administered rabbits were observed. Intravitreal injections of SMAP and anti-SMAP antibodies to MIAA-administered rabbits resulted in significant upregulation of the rhodopsin (P < 0.001) and HSP70 (P < 0.001) contents in the retina. Downregulation of titers of natural autoimmune anti-SMAP antibodies in blood serum of the RP-diagnosed patients relative to those in healthy persons of the same age (P < 0.01) was seen. Molecular mechanisms underlying the hypothalamic serotonergic trophic regulatory effects on retinal receptor cells through retrograde and anterograde axonal transports are discussed. Ausführliche Beschreibung