Comparison of retinal gene expression among Chx10-cre;Tsc f/f, Chx10-cre;Tsc+/+ and 24-month-old C57BL/6 mice

Retina aging is the main cause of vision decline in elderly population and it is also an important risk factor for the development of degenerative and angiogenic retinal diseases. Therefore it is important to explore the mechanisms which drive retina aging. In this study, we found that retina from old-aged mice had increased mTORC1 activity. Whole transcriptome microarray expression profiling of the retina tissue among among Wild Type Control, Chx10-specific Tsc1 knockout and natural aging mice showed that the most significantly enriched Gene Ontology terms were substantially in common in knockout and aging mice compared to Control mice. we further demonstrated that the activation of mTORC1 in Chx10-expressing cells led to accelerated retina aging and degeneration, with significant functional decline measured by electroretinogram, ganglion cell senescence, microglial cell activation and the accumulation of oxidative stress and inflammatory responses. Inhibition of microglial cells by minocycline partially prevented photoreceptor cell loss and restored the electroretinogram responses. The results demonstrated that mTORC1 activation accelerated retina aging, suggested that microglial cell contributed significantly to overall retinal degeneration. Retinal mRNA profiles of 5-month-old Chx10-cre;Tsc1f/f mice, age-matched Wild Type Control mice and 24-month-old C57BL/6 mice were generated by transcriptome microarray. Three independent experiments were performed for knockout and Control group, and 2 for C57-old group in the study