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M.M. Sohocki, K. Bevington; Pinealocyte expression of retinopathy genes: a role in circadian rhythm abnormalities? . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5284.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Mutations in several genes with expression limited to the photoreceptors and pinealocytes, such as the cone–rod homeobox gene (CRX), peripherin/RDS, and the gene encoding the aryl–hydrocarbon receptor interacting protein (AIPL1), are known to cause inherited retinopathy. Patients with mutations in these genes frequently cite secondary symptoms such as severe sleep abnormalities, or insomnia, but these complaints are often dismissed as due to limited physical activity in blind individuals. Due to the embryological, structural, and functional relationship of the photoreceptors and pinealocytes, it is possible that mutations causing photoreceptor degeneration in these patients might impact pineal function, resulting in abnormal circadian entrainment and these secondary symptoms. However, it is unknown how many retinopathy genes are also pineal–expressed or how many patients could be affected; therefore, we sought to determine which of the known retinopathy genes are pineal expressed. Methods:The literature concerning each known retinopathy gene was studied to determine if the sequence was assayed for pineal expression. For genes not assayed in the pineal, publicly available EST databases (TIGR, GenBank) were searched for pineal ESTs arising from the gene. For all genes that were not shown by these methods to have pineal expression, a human pineal gland cDNA library (B. Soares) was screened by PCR. Results:Pineal expression of thirty–five known retinopathy genes was detected. The retinopathies associated with these genes include LCA, BBS, RP, CSNB, CORD, LHON, optic atrophy, Refsum Disease, Batten Disease, and achromatopsia. Conclusions:Roughly one–third of retinopathy genes are expressed in the pineal gland, indicating a large number of individuals potentially affected with circadian rhythm abnormalities secondary to their retinal disease. These results will make possible comparison of circadian rhythm in patients whose circadian rhythm may be abnormal due to pineal involvement to that of control individuals, whose retinopathy is caused by mutations in genes that are retina–specific. If future studies support the hypothesis that circadian abnormalities in these patients are caused by the pineal involvement, studies into the ability of melatonin therapy to alleviate the symptoms in this group of patients will be possible.
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