Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina

Caroline W. Little, Bienvenido Castillo, David A. DiLoreto, Christopher Cox, Jeffrey Wyatt, Coca Del Cerro, Manuel Del Cerro

Research output: Contribution to journalArticle

Abstract

Purpose. The Royal College of Surgeons (RCS) rat suffers from a well- characterized, early-onset, and relentless form of photoreceptor cell degeneration. It has been shown that allografts of retinal pigment epithelial cells from normal perinatal rats have rescue effects in this condition. In preparation for human application, the authors determined whether human fetal retinal pigment epithelium (RPE) grafts have a photoreceptor rescue effect in RCS dystrophic rat retinas. Methods. Sheets of RPE from human fetal eyes (10 to 16 weeks gestational age) were isolated according to the authors' recently described method. Fragments of the RPE sheets were transplanted to the subretinal space within the superior hemisphere. Transplants were performed within the superior equatorial region of five dystrophic RCS rats, one eye per animal. A similar volume of vehicle was injected into the subretinal space of five age-matched control rats, again one eye per rat. All rats were immunosuppressed with daily injections of cyclosporine. Using light microscopy, photoreceptor cell nuclear profiles of superior equatorial (SE) and inferior equatorial (IE) regions of transplanted and sham-injected control animals were counted. Results. Four weeks after transplantation, a dramatic rescue effect was observed. Microscopically, presumptive donor RPE cells were seen as single pigmented cells and as cell clusters in the subretinal space. An outer nuclear layer three to four profiles thick was present in the area of the RPE transplant but was nearly absent in the rest of the retina, as well as in the retinas of control rats. The number of photoreceptor nuclear profiles per 100 μm was 34.7 ± 2.2 (mean ± SEM) in the SE region of transplanted rats and 3.5 ± 1.4 in the same region of sham- injected rats. There were 3.0 ± 1.0 photoreceptor nuclear profiles in the IE region of transplanted rats and 3.5 ± 1.2 in the IE region of sham-injected eyes. No evidence of graft rejection was seen. Conclusions. This study provides the first indication that transplanted human fetal RPE cells are able to rescue photoreceptor cells in a model of hereditary retinal degeneration.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number1
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • human fetal tissue
  • photoreceptor rescue
  • retinal degeneration
  • retinal pigment epithelium
  • transplantation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina'. Together they form a unique fingerprint.

  • Cite this