Thinning of the RPE and choroid associated with T lymphocyte recruitment in aged and light-challenged mice

Mol Vis. 2015 Sep 2:21:1051-9. eCollection 2015.

Abstract

Purpose: Thinning of the RPE and the underlying vascular layer, the choroid, is observed with age in many human eye disorders. The reasons for this thinning are ill-defined. Here, we highlight the possible role of T lymphocyte recruitment in choroidoretinal thinning in aged and light-challenged mice.

Methods: In age and light challenge models, we measured chemokine concentrations using enzyme-linked immunosorbent assay and used flow cytometry to characterize lymphocyte populations. We quantified thinning in eye immunosections and RPE65 expression using quantitative PCR.

Results: Age and light challenge led to increased levels of the lymphotactic protein CXCL10 alone (aging) or in conjunction with CXCL9 (light challenge). Increased numbers of CD3+ T lymphocytes, most of them CD8+ cytotoxic T lymphocytes, were also observed in the choroid and retina of old mice and following light challenge. Influx of T lymphocytes was associated with RPE and choroidal thinning and diminished expression of RPE65 mRNA, an essential enzyme of the visual cycle.

Conclusions: The observations from this study suggest that cytotoxic CD8(+) T lymphocytes might participate in choroidal and RPE degeneration and that modulation of T lymphocyte recruitment might be a novel strategy to reduce choroidoretinal dysfunctions observed with age and following photo-oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / immunology
  • Aging / pathology
  • Animals
  • Cell Movement / radiation effects
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / immunology
  • Choroid / immunology
  • Choroid / pathology
  • Choroid / radiation effects*
  • Gene Expression Regulation
  • Humans
  • Light / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Photochemical Processes
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology
  • Retinal Pigment Epithelium / immunology
  • Retinal Pigment Epithelium / pathology
  • Retinal Pigment Epithelium / radiation effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Cytotoxic / radiation effects*
  • cis-trans-Isomerases / genetics*
  • cis-trans-Isomerases / immunology

Substances

  • CXCL10 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • RNA, Messenger
  • retinoid isomerohydrolase
  • cis-trans-Isomerases