Retinal sheet transplantation in rats with retinal degeneration restores visual cortical responses

• Autorzy: Foik T.A. , Lean G.A. , McLelland B.T. , Mathur A. , Aramant R.B. , Seiler M. , Lyon D.C.
• Języki publikacji: EN

Abstrakty

EN

Age related macular degeneration and retinitis pig‑ mentosa lead to a profound loss of vision in millions of people worldwide. Many of these patients lose both retinal pigment epithelium (RPE) and photoreceptors. Fetal derived retinal progenitor sheets have been suc‑ cessfully transplanted into both rodents (review: Seiler and Aramant, 2012 Prog Retin Eye Res, 31:66187) and hu‑ mans (Radtke et al, 2008 Am J Ophthalmol, 146:172182). In several models of retinal degeneration (RD), trans‑ plants restore rudimentary responses to flashes of light in a region of the superior colliculus (SC) correspond‑ ing to the location of the transplant in the host retina; and synaptic connectivity between transplant and RD host retina has been confirmed. However, in order to determine the quality and accuracy of visual informa‑ tion provided by the transplant, here we study visual responsivity at the level of visual cortex where higher visual perception is processed. Specifically, we used the transgenic Rho S334ter3 RD rat, which begins to lose photoreceptors at an early age, becoming blind shortly after one month postnatal. Between 24-40 days of age, RD rats received fetal rat retinal sheet transplants in one eye. Donors were rats expressing human placental alkaline phosphatase in all cells. Three to ten months following surgery, we found several neurons in the re‑ gion of primary visual cortex (V1) matching the trans‑ planted portion of the retina that were well tuned to stimulus orientation, size, contrast, and spatial and temporal frequency. Each of these response features are considered fundamental properties of V1 neurons that are necessary building blocks for higher level vi‑ sual processing, such as shape and motion perception. In addition, we find that these response properties are absent in nontransplanted and sham transplanted RD rats, but are on par with normal age matched controls that do not suffer from RD. Moreover, in rats with nor‑ mal retinas and RD rats with retinal transplants spon‑ taneous firing rates were low, whereas in the RD rats without transplants spontaneous firing rates were of‑ ten higher, indicating abnormal function in the absence of visual input. In conclusion, our data thus far indicate that fetal rat retinal sheet transplants can restore vi‑ sual cortical responses in transgenic RhoS334ter3 RD rats. This restoration of ‘normal’ cortical physiology in a rat model represents a critical step towards develop‑ ing an effective remedy for the visually impaired hu‑ man population.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2018
• Tom: 78
• Numer: Suppl.1
• Opis fizyczny: p.18

Twórcy

autor

Foik T.A.

autor

Lean G.A.

autor

McLelland B.T.

• Department of Physical Medicine and Rehabilitation, University of California, Irvine, CA, USA

autor

Mathur A.

• Department of Physical Medicine and Rehabilitation, University of California, Irvine, CA, USA

autor

Aramant R.B.

• Department of Physical Medicine and Rehabilitation, University of California, Irvine, CA, USA

autor

Seiler M.

• Department of Physical Medicine and Rehabilitation, University of California, Irvine, CA, USA

autor

Lyon D.C.