A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. (23rd May 2018)

• Record Type: Journal Article
• Authors: Bell, W. Robert; Meeker, Alan K.; Rizzo, Anthony; Rajpara, Sumit; Rosenthal, Ian M.; Flores Bellver, Miguel; Aparicio Domingo, Silvia; Zhong, Xiufeng; Barber, John R.; Joshu, Corinne E.; Canto‐Soler, M. Valeria; Eberhart, Charles G.; Heaphy, Christopher M.
• Is Part Of: Brain pathology. Volume 29:Number 1(2019)
• Page Start: 45
• Page End: 52
• Publication Date: 2018-05-23
• Subjects: diabetic retinopathy -- glaucoma -- retina -- rod photoreceptors -- telomeres; Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12618
• Languages: English
• ISSNs: 1015-6305

Abstract

Abstract: We have identified a discrete, focal telomere DNA expansion phenotype in the photoreceptor cell layer of normal, non‐neoplastic human retinas. This phenotype is similar to that observed in a subset of human cancers, including a large fraction of tumors of the central nervous system, which maintain their telomeres via the non‐telomerase‐mediated alternative lengthening of telomeres (ALT) mechanism. We observed that these large, ultra‐bright telomere DNA foci are restricted to the rod photoreceptors and are not observed in other cell types. Additionally, focus‐positive rod cells are dispersed homogeneously throughout the posterior retinal photoreceptor cell layer and appear to be human‐specific. We examined 108 normal human retinas obtained at autopsy from a wide range of ages. These large, ultra‐bright telomere DNA foci were not observed in infants before 6 months of age; however, the prevalence of focus‐positive rod cells dramatically increased throughout life. To investigate associations between this phenotype and retinal pathology, we assessed adult glaucoma (N = 29) and diabetic retinopathy (N = 38) cases. Focus‐positive rod cells were prominent in these diseases. When compared to the normal group, after adjusting for age, logistic regression modeling revealed significantly increased odds of falling in the high category of focus‐positive rod cells for glaucoma and diabetic retinopathy. In summary, we have identified a dramatic telomere alteration associated with aging and diseases affecting the retina.