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L. Giummarra, M. J. Murphy, M. J. Goodyear, S. G. Crewther; Microarray Analysis of Chick Retina/RPE/Choroid During Recovery From Form Deprivation Myopia (FDM). Invest. Ophthalmol. Vis. Sci. 2010;51(13):1674.
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Blindness due to complications secondary to myopia such as glaucoma, retinal detachment and retinal and cystic edema are all associated with perturbed water balance both within the retina and ocular globe. It is expected that osmoregulatory genes such as endothelin-1 as well as cation channels will be up-regulated as the eye recovers from lack of form vision. To test this hypothesis, microarray analysis of mRNA from chick retina/RPE/choroid was conducted.
Male Leghorn x New Hampshire Australorp chicks were monocularly occluded for 10 days to induce a myopic state. Chicks were then given normal visual experience from day 11 for 0hrs, 6hrs and 24hrs to initiate refractive recovery. Eyes were measured with retinoscopy and A-scan ultrasonography. RNA was then isolated from retina/RPE/choroid for microarray analysis by Affymetrix gene-chip array. Data analysis was conducted using Pathway Studio 7.0 to determine significant regulatory changes.
Form deprivation induced abnormal axial and vitreous chamber elongation that decreased as expected across the recovery period. Microarray analysis showed an upregulation of endothelin (END1), cation homeostasis, serum/glucocorticoid kinase (SGK) and myeloid/lymphoid leukaemia 3 (MLL3) mRNA during the 24hr recovery period.
Analysis of mRNA changes during FDM implicates a role for genes associated with reperfusion injuries caused by blood-retinal-barrier (BRB) breakdown, leading to abnormal vascularisation and edema during the recovery response. END1 increases BRB permeability and thus edema formation. Cation channels were upregulated 6 hours after occluder removal, indicating the presence of general oxidative stress and the upregulation of SGK until choriocapillaris function returns to normal after 24 hours post FDM. Upregulation of SGK and MLL3 is known to accompany not only increased K channel expression but also Cl and Na channels to regulate cellular hydration or swelling. Thus, the importance of retinal/RPE/choroid osmoregulatory processes is vital during recovery from FDM.
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