Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses

Invest Ophthalmol Vis Sci. 2007 Feb;48(2):916-26. doi: 10.1167/iovs.06-0811.

Abstract

Purpose: Subretinal prosthetics are designed to electrically stimulate second-order cells, replacing dysfunctional photoreceptors in diseases such as retinitis pigmentosa (RP). For functional vision to occur, this signal must also reach central visual structures. In the current study, a subretinally implanted prosthetic was evaluated in the Royal College of Surgeons (RCS) rat model of RP, to determine its capacity to activate the retinotectal pathway.

Methods: Prosthetic implants were placed in RCS and wild-type (WT) rats at 4 weeks of age and evaluated 3 months later. Control rats underwent sham surgery, implantation with inactive prosthetics, or no treatment. Implant- and visible-evoked responses were isolated and evaluated in the superior colliculus (SC).

Results: In WT and RCS rats with active prosthetics, implant-driven responses were found in 100% of WT and 64% of RCS rats and were confined to a small SC region that corresponded to the retinal sector containing the implant and differed from visible-evoked responses. In addition, visible-evoked responses were more robust at sites that received implant input compared to sites that did not. These effects were not seen in WT rats or RCS control animals; although a general trophic effect on the number of responsive sites was observed in all RCS rats with surgery compared to untreated RCS rats.

Conclusions: Direct activation of the retina by a subretinal implant induces activity in the SC of RCS rats, suggesting that these implants have some capacity to replace dysfunctional photoreceptors. The data also provide evidence for implant-induced neurotrophic effects as a consequence of both its presence and its activity in the retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Electric Stimulation Therapy / methods*
  • Electrodes, Implanted*
  • Evoked Potentials, Visual / physiology*
  • Microelectrodes
  • Photic Stimulation
  • Prosthesis Implantation*
  • Rats
  • Rats, Long-Evans
  • Rats, Mutant Strains
  • Retina / physiopathology*
  • Retinitis Pigmentosa / physiopathology*
  • Retinitis Pigmentosa / surgery
  • Superior Colliculi / physiology
  • Visual Pathways / physiology*