Figure 3.

Dose-dependent effects of pEYS611 administration in the rat light-induced damage (LID) model. Rats received a single ciliary muscle electrotransfection of pEYS611 at the dose of 0.3, 3, or 30 µg/eye on day (-) 3 (D-3) or left untreated (n = 8 animals/group). Except for the unexposed animals (no LID), retinal degeneration was induced on D0 by 24 h of bright light exposure (6500 lux). Dark- and light-adapted electroretinography (ERG) responses were recorded simultaneously from both eyes on D8. Following ERG recordings, animals were sacrificed for analysis of human TF levels in ocular fluids and histological evaluations. (A) Representative images of retina section (superior pole) stained with hematoxylin eosin. Scale bar, 50 µm. (B) ONL thickness was measured every 500 µm from the optic nerve (0) to the inferior (−) and superior (+) poles of the retina. Compared with no LID control animals, the ONL of LID/untreated animals was thinner. Treatment with pEYS611 resulted in a dose-dependent preservation of the ONL, correlating with human TF levels measured in ocular fluids (C). (D) Representative images of cone-arrestin staining at a distance of 1500–2000 µm from the optic nerve in the superior part of the retina (4.6-diamidino-2-phenylindole (DAPI) in blue/cone arrestin in green). Scale bar, 25 µm. (E) The number of cone-arrestin-positive cells per retinal section was significantly higher in LID/pEYS611-treated animals compared to LID/untreated rats. All values are presented as mean ± sem. * p < 0.05; *** p < 0.001 using Dunn’s multiple comparisons test versus LID/untreated group. IS, inner segment; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segment.