Anti‐inflammatory and anti‐apoptotic activity of a TSPO ligand in slowing retina neurodegeneration in a model of retinitis pigmentosa

Abstract

Aims/Purpose: An evolutionary well‐conserved protein called translocator protein (TSPO, 18 kDa) is found on the outer mitochondrial membrane. Under typical physiological conditions, TSPO expression in the central nervous system is rather low. Changes in TSPO expression, however, can result from several clinical conditions, including neurodegenerative diseases, and neuroinflammation. In a previous study (1) we test the efficacy of a new class of TSPO ligands (PIGAs) (1), in an in vitro model (661W, photoreceptor‐like cell line) of Lipopolysaccharide (LPS)‐induced neuroinflammation. We demonstrate the TSPO expression in retinal photoreceptor and the activity of this ligands in an in vitro neurodegeneration. Here, we examined the anti‐inflammatory effects of the highest active TSPO ligand (PIGA‐1138) on heterozygous (±) Tvrm4 mice (RhoTvrm4/Rho+) an animal model of autosomal dominant retinitis pigmentosa (RP) highly sensitive to light‐induced photoreceptor degeneration. The inflammatory component plays a predominant role in RP progression towards cone death and complete blindness.Methods: Mice have been treated with 3 or 10 mg/kg/die for seven days, starting from the day of onset of retinal degeneration induced by exposure for 1 min to a white light of 12000lux intensity. At the end of the protocol retinal functionality was tested by recording Electroretinogram (ERG) flash response in both scotopic and photopic conditions. Retinal tissue was collected from recorded mice and the tissue was used for further analyses including biochemical and molecular biology assays.Results: PIGA‐treated animal group shows improved response to flash ERG, reduced damaged area measured by cone‐arrestin staining, and modulation of pro‐ and anti‐inflammatory markers.Conclusions: As conclusion, we were able to establish that the TSPO ligand can slow down photoreceptor degeneration and confirm the results of the in vitro study.