June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Electrophysiological evidence for connectivity of fetal retinal sheet transplant in a novel immunodeficient retinal degenerate rat model
Author Affiliations & Notes
  • Robert Lin
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Alexander De Guzman
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Bibo Khatib
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Bryce T McLelland
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Anuradha Mathur
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Leonard Kitzes
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Biju B Thomas
    Ophthalmology, USC, Los Angeles, CA
  • Robert B Aramant
    Stem Cell Research Center, UC Irvine, Costa Mesa, CA
  • Magdalene J Seiler
    Physical Medicine & Rehabilitation, UC Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Robert Lin, None; Alexander De Guzman, None; Bibo Khatib, None; Bryce McLelland, None; Anuradha Mathur, None; Leonard Kitzes, None; Biju Thomas, None; Robert Aramant, Ocular transplantation LLC (E), Ocular transplantation LLC (P); Magdalene Seiler, Ocular transplantation LLC (C), Ocular transplantation LLC (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1823. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Robert Lin, Alexander De Guzman, Bibo Khatib, Bryce T McLelland, Anuradha Mathur, Leonard Kitzes, Biju B Thomas, Robert B Aramant, Magdalene J Seiler; Electrophysiological evidence for connectivity of fetal retinal sheet transplant in a novel immunodeficient retinal degenerate rat model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1823.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract
 
Purpose
 

Retinal degenerative (RD) diseases such as age related macular degeneration and retinitis pigmentosa cause a gradual loss of vision and have no effective treatment. Previously we have established a transplantation protocol for fetal retinal sheets in the S334ter line-3 RD rat model. The present study provides electrophysiological evidence that implanted fetal retinal sheets restore light response in a novel immunodeficient S334ter line-3 RD rat model (SD-Foxn1 Tg(S334ter)3Lav).

 
Methods
 

Control, non-RD rats were compared to immunodeficient S334ter line 3 RD rats (P30-P40) that were transplanted with intact fetal retinal sheets in the subretinal space. The size and location of the transplant was followed using OCT before electrophysiological testing. Prior to electrophysiological testing, rats were dark-adapted overnight. Transplanted rats were anesthetized, a craniotomy was performed, and the superficial layer of the superior colliculus (SC) was exposed. Single and multi-unit responses to a 40ms 6.5mcd/m2 light flash were recorded from locations in SC approximately 200μm apart. Responses were analyzed using a custom Matlab program.

 
Results
 

OCT scans indicated that the placement of the retinal sheet transplants remained constant and were located in the subretinal space between the retinal pigment epithelium and the host retina. In control rats, visual responses were robust in all areas of the SC. However, in the immunodeficient S334ter rat the same stimulus was unable to elicit a response in most of the SC recording sites. Interestingly, robust responses were observed in a cluster of recording sites that were all within several hundred microns of each other.

 
Conclusions
 

Fetal retinal sheet transplants were stable for several months in immunodeficient S334ter rats and did not display any signs of host-graph rejection. The location of responses to light in the SC corresponded to transplant location in the retina. These data suggest that retinal sheet transplants are capable of integrating and surviving in the retina of immunodeficient rats. Additionally, the integration of the transplant into the retina of these animals is sufficient to restore light response in the SC.  

 
Spike counts recorded from the SC of an immunodeficient S334ter line 3 RD rat two months post-retinal sheet transplantation indicate a localized region of activity.
 
Spike counts recorded from the SC of an immunodeficient S334ter line 3 RD rat two months post-retinal sheet transplantation indicate a localized region of activity.

 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×