Form Deprivation Modulates Retinal Neurogenesis in Primate Experimental Myopia

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 12; pp. 4681 - 4686
• Main Authors: Tkatchenko, Andrei V., Walsh, Pamela A., Tkatchenko, Tatiana V., Gustincich, Stefano, Raviola, Elio
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 21.03.2006; National Acad Sciences
• Subjects: Amacrine cells; Animals; Biological Sciences; Cell division; Cell Division - genetics; Cell growth; Cell Proliferation; Deoxyribonucleic acid; DNA; Eyes; Eyes & eyesight; Gene Expression; Genes; Haplorhini; Macaca mulatta; Molecular Sequence Data; Monkeys & apes; Myopia; Myopia - genetics; Neural stem cells; Neurons; Neurons, Afferent - cytology; Neurons, Afferent - metabolism; Neurosciences; Oligonucleotide Array Sequence Analysis; Peptides; Photoreceptors; Retina; Retina - cytology; Retina - growth & development; Retina - metabolism; Sensory Deprivation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Vasoactive Intestinal Peptide - genetics; Vasoactive Intestinal Peptide - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600589103

Juvenile primates develop myopia when their visual experience is degraded by lid fusion. In response to this abnormal visual input, retinal neural networks cause an excessive growth of the postequatorial segment of the eye, but the mechanism underlying this axial elongation is unknown. After fusion of the lids in one eye of juvenile rhesus macaques and green monkeys, we combined cDNA subtractions, microarray profiling, and real-time PCR to compare gene expression in the retinas of the closed and open eyes. This molecular analysis showed up-regulation of a number of genes associated with cell division in the retina of the closed eye and differential expression of six genes localized to chromosomal loci linked to forms of human hereditary myopia. In addition, it substantiated a previous observation, based on immunocytochemistry, that synthesis of vasoactive intestinal polypeptide was increased upon lid fusion. Injection of 5-bromo-2'-deoxyuridine and immunocytochemistry showed that the primate retinal periphery harbors mitotically active neuroprogenitor cells that increase in number when the visual experience is altered by lid fusion. Furthermore, the number of dividing cells is highly correlated with axial elongation of the eye and the resulting myopic refractive error. Thus, the retina undergoes active growth during the postnatal development of the primate eye. This growth is modulated by the visual input and accelerates considerably when the eye develops axial myopia. Vasoactive intestinal polypeptide may be the molecule that stimulates retinal growth.