April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Intravitreal CNTF Injection Leads to Reversible Photoreceptor Deconstruction in the Normal Canine Retina
Author Affiliations & Notes
  • Andras M. Komaromy
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Jessica S. Rowlan
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Amanda T. Parton Corr
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Shelby L. Reinstein
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Britt Levy
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Rong Wen
    Bascom Palmer Eye Inst, University of Miami, Miami, Florida
  • William A. Beltran
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
  • Gustavo D. Aguirre
    Clinical Studies, Univ of Pennsylvania, Sch of Vet Med, Philadelphia, Pennsylvania
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4341. doi:
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      Andras M. Komaromy, Jessica S. Rowlan, Amanda T. Parton Corr, Shelby L. Reinstein, Britt Levy, Rong Wen, William A. Beltran, Gustavo D. Aguirre; Intravitreal CNTF Injection Leads to Reversible Photoreceptor Deconstruction in the Normal Canine Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4341.

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

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Abstract

Purpose: : To evaluate the short-term effects of a single intravitreal CNTF injection on the structure, function, and gene expression pattern in normal canine retinas.

Methods: : Normal, adult dogs were injected intravitreally with 12 µg of human recombinant CNTF; contralateral eyes served as controls and were injected with a similar volume of PBS. Retinal function (flash ERG), morphology (LM, EM), gene (qRT-PCR) and protein expression (immunohistochemistry and western blotting) were evaluated at 1, 2, and 5 weeks post injection.

Results: : One week after CNTF injection both scotopic and photopic ERG responses were almost completely extinguished. The ERG amplitudes partially recovered by 2 weeks, and completely restored by 5 weeks post injection. The transient functional loss at 1 week was associated with a drastic but reversible shortening and disorganization of photoreceptor inner and outer segments. Expression of photoreceptor-specific genes, e.g. opsins and cyclic nucleotide-gated channel subunits, was significantly reduced at 1 week, but subsequently recovered. While most of these mRNA reductions were between 68 - 84%, S-opsin expression was more severely affected with a 99.99% decrease. There was a marked increase in phosphor-STAT3 at 1 week in the outer nuclear, inner nuclear, and ganglion cell layers. This increase was more moderate for phosphor-STAT1. The amounts of both phosphor-STAT1 and phosphor-STAT3 gradually declined and returned to the control levels by 5 weeks post injection.

Conclusions: : Intravitreal injection of CNTF protein leads to reversible biochemical and structural changes, as well as decreases in photo-responsiveness of rods and cones in the normal canine retina. This process is likely mediated by activation of the Jak/STATs pathways.

Keywords: cytokines/chemokines • drug toxicity/drug effects • photoreceptors 
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