Transcriptome comparison between Old vs young rat retinae

Visual decline in the elderly is often attributable to retinal aging, which predisposes the tissue to pathologies including age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. Utilizing the Fischer 344 rat model of aging, we evaluated the efficacy of 8-aminoguanine (8-AG), a compound previously shown for multi-organ protection, against age-related retinal degeneration. Remarkably, administration of 8-AG at a dosage of 5 mg/kg body weight via drinking water from 22 months of age for a duration of 8 weeks resulted in substantial retinal preservation evidenced by an increase in retinal thickness, a greater number of photoreceptors with longer outer segments, and enhanced electroretinogram signals. RNA sequencing and subsequent analyses revealed pronounced anti-inflammatory effects by 8-AG on both adaptive and innate immune responses within the aged retina. Overall design: To compare the transcriptome changes affected by aging and by 8-AG treatment, we collected retina and RPE/choroids separetly from young (4 months old), aged (24 months old) and 8-AG treated (24 months old) Fischer344 rats. Specifically, 5 mg/kg body weight of 8-AG was treated daily to the aged rats starting at 22 monthls of age by suppementing the compound in the drinking water. The drinking water was refresehd daily and the treatment lasted 8 weeks and animals were euthanized at 24 months of age for tissue collection. mRNA seq was performed for both retina and RPE/choroids samples.