Environmental enrichment extends photoreceptor survival and visual function in a mouse model of retinitis pigmentosa

PLoS One. 2012;7(11):e50726. doi: 10.1371/journal.pone.0050726. Epub 2012 Nov 28.

Abstract

Slow, progressive rod degeneration followed by cone death leading to blindness is the pathological signature of all forms of human retinitis pigmentosa (RP). Therapeutic schemes based on intraocular delivery of neuroprotective agents prolong the lifetime of photoreceptors and have reached the stage of clinical trial. The success of these approaches depends upon optimization of chronic supply and appropriate combination of factors. Environmental enrichment (EE), a novel neuroprotective strategy based on enhanced motor, sensory and social stimulation, has already been shown to exert beneficial effects in animal models of various disorders of the CNS, including Alzheimer and Huntington disease. Here we report the results of prolonged exposure of rd10 mice, a mutant strain undergoing progressive photoreceptor degeneration mimicking human RP, to such an enriched environment from birth. By means of microscopy of retinal tissue, electrophysiological recordings, visual behaviour assessment and molecular analysis, we show that EE considerably preserves retinal morphology and physiology as well as visual perception over time in rd10 mutant mice. We find that protective effects of EE are accompanied by increased expression of retinal mRNAs for CNTF and mTOR, both factors known as instrumental to photoreceptor survival. Compared to other rescue approaches used in similar animal models, EE is highly effective, minimally invasive and results into a long-lasting retinal protection. These results open novel perspectives of research pointing to environmental strategies as useful tools to extend photoreceptor survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Ciliary Neurotrophic Factor / genetics
  • Disease Models, Animal
  • Female
  • Male
  • Mice
  • Photoreceptor Cells, Vertebrate / cytology*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / physiology*
  • Physical Stimulation*
  • Retina / pathology
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / therapy*
  • TOR Serine-Threonine Kinases / genetics

Substances

  • Ciliary Neurotrophic Factor
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the Italian National Research Council, CNR (www.cnr.it), the Velux Foundation project 691 to ES (http://www.veluxstiftung.ch/home/en-index.php), the PNR-CNR Aging Program 2012–2014, and the University of Pisa (www.unipi.it). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.