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Transcriptome comparison between Old vs young rat retinae

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE254123 | GEO | 2024/05/31

REPOSITORIES: GEO

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Project description:This study utilized a standard rat model of aging and global gene expression analyses to attempt to identify the most appropriate time points to study vascular aging and to identify molecules associated with the development of pathology. Recent studies have established that age is the major risk factor for vascular disease. Numerous changes occur in vascular structure and function during aging, and animal models, including rodents, are the primary means to determine the underlying mechanisms of age-mediated vascular pathology. This study utilized a standard rat model of aging and both morphometric and global gene expression analyses to attempt to identify the most appropriate time points to study vascular aging and to identify molecules associated with the development of pathology. Morphometric analysis of Fischer 344/Brown Norway F1 hybrid (F344xBN) rat thoracic aorta indicated, in contrast to some previous studies, that progressive increases in intimal and medial thickness, as well as smooth muscle cell-containing intimal protrusions, occurred with age. This structural vascular pathology was associated with a progressive increase in global differential gene expression. Specific molecules with altered mRNA and protein expression included the adhesion molecules ICAM-1 and VCAM-1, and the bone morphogenic proteins osteopontin and bone sialoprotein-1. Intimal-associated macrophages were detected with immunohistochemistry in paraffin sections of thoracic aorta and were found to increase significantly in number with age. Both systemic and tissue markers of oxidant stress, serum 8-isoprostane and 3-nitrotyrosine, respectively, were found to increase during aging. The results demonstrate that increased inflammation and oxidant stress occur progressively during vascular aging, and suggest therapeutic targets to limit or reverse aging-associated vascular pathology and dysfunction. Experiment Overall Design: Samples were taken from rats at 4 ages, 3mo, 6mo, 15mo and 28 mo, with 4 replicates in each age group.

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Transcriptome comparison between Old vs young rat retinae

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