A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease

William Robert Bell, Alan K. Meeker, Anthony Rizzo, Sumit Rajpara, Ian M. Rosenthal, Miguel Flores Bellver, Silvia Aparicio Domingo, Xiufeng Zhong, John R. Barber, Corinne E. Joshu, M. Valeria Canto-Soler, Charles G. Eberhart, Christopher M. Heaphy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalBrain Pathology
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Retinal Rod Photoreceptor Cells
Telomere
Phenotype
DNA
Retina
Diabetic Retinopathy
Glaucoma
Accidental Falls
Telomere Homeostasis
Central Nervous System Neoplasms
Photoreceptor Cells
Vertebrate Photoreceptor Cells
Autopsy
Logistic Models
Pathology
Neoplasms

Keywords

  • diabetic retinopathy
  • glaucoma
  • retina
  • rod photoreceptors
  • telomeres

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Bell, W. R., Meeker, A. K., Rizzo, A., Rajpara, S., Rosenthal, I. M., Flores Bellver, M., ... Heaphy, C. M. (2019). A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. Brain Pathology, 29(1), 45-52. https://doi.org/10.1111/bpa.12618

A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. / Bell, William 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.

In: Brain Pathology, Vol. 29, No. 1, 01.01.2019, p. 45-52.

Research output: Contribution to journalArticle

Bell, WR, Meeker, AK, Rizzo, A, Rajpara, S, Rosenthal, IM, Flores Bellver, M, Aparicio Domingo, S, Zhong, X, Barber, JR, Joshu, CE, Canto-Soler, MV, Eberhart, CG & Heaphy, CM 2019, 'A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease', Brain Pathology, vol. 29, no. 1, pp. 45-52. https://doi.org/10.1111/bpa.12618
Bell, William 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. / A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. In: Brain Pathology. 2019 ; Vol. 29, No. 1. pp. 45-52.
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