Inflammation is established as a key factor in mediating the progression of a number of retinal degenerations, including both wet and dry age-related macular degeneration (AMD) [1-3]. MicroRNAs (miRNAs) are a class of endogenously occurring non-coding RNA (ncRNA) molecules that are gaining momentum as therapeutic targets for treating a number of human conditions [4-6] and have been identified to modulate inflammation [7]. The purpose of this study is to investigate the modulation of miRNAs in a

more »

... model of retinal degeneration, the light damage model. MiRNA and their potential roles in mitigating retinal inflammation will also be investigated in animals treated with 670nm red light therapy. Albino rats raised in dim cyclic light conditions (5lux; 12hr on, 12hr off; controls) were exposed to bright continuous light (1000lux) for 24 hours and returned to dim light conditions for 0, 3 or 7 days. At each timepoint animals were culled and their eyes removed and processed either for histological analyses or RNA based analyses. For histology eyes were fixed in 4% paraformaldehyde, cryoprotected and sectioned to determine the photoreceptor cell death using TUNEL or perform immunohistochemistry experiments using Vimentin and IBA1 or in situ hybridisation for Ccl2 and miR-124-3p. RNA was extracted from dissected retinas, reverse transcribed and used for low density array and qPCR analysis to determine the expression changes of genes and miRNAs. Immortalised cell lines were also used for performing cell transfections and similar RNA based analyses as above. Intense light exposure for 24 hours led to differential expression of a number of miRNAs, 37 of which were significantly modulated by 2-fold or more. Of those, 19 may potentially regulate the inflammatory immune response observed in the model. MicroRNAs -125-3p, -155, -207, -347, -449a, -351, and -542-3p are all upregulated at 24 hours of exposure along with peak photoreceptor cell death. The miRNAs -542-3p and -351 reached maximum expression at 7 days after exposure, while [...]