Aging and retinal degeneration in rod photoreceptors: system biology to detect stochastic functional changes

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NEI	DEV-3

Authors

• N Gotoh
• L Gieser
• R Villasmil
• H Rajasimha
• R Cojocaru
• T Cogliati
• A Swaroop

Abstract

Early intervention in retinal degeneration and age related macular degeneration (AMD) is one of the major issues in ophthalmology. Aging is the major risk factor for AMD, with rod photoreceptors displaying vulnerability early in the aging process. Furthermore, rod photoreceptors are good therapeutic targets since, irrespective of the genetic mutation, the earliest degeneration changes occur in this cell type. We adopted a system biology approach to identify early biomarkers and pathways driving the molecular and functional changes in these conditions. Several mouse models were used, including rd1, rdS, rd10, rd16. Gene expression profiles were also generated for Nrlp-eGFP mice, starting at embryonic day (E)14, to 18 months of age. Rods were purified from Nrlp-eGFP wild type and mutant mice using flow cytometry (Akimoto et al. 2006). Extracted total RNA including microRNA was analyzed using Affymetrix GeneChip mouse Exon 1.0 ST arrays. Quality control and data analysis were performed using several computational approaches and commercial packages. The microarray dataset generated using samples from retinal degeneration mice yielded 1,878,352 data points, whereas the same technology yielded 2,331,169 data points when samples of aging wild type mice were analyzed.

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