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Abstract
Purpose: To examine retinal function after the long-term, gene therapy–delivered expression of exogenous glial cell line–derived neurotrophic factor (GDNF). Methods: Forty Sprague-Dawley rats each received an intravitreal injection of recombinant adeno-associated virus expressing GDNF (rAAV-GDNF) in their right eye. The left eye was untreated. One year after viral transduction in ocular tissues, retinal morphology and function were compared between rAAV-GDNF–injected and normal naïve eyes. Synthesis and accumulation of GDNF within the retina were immunohistologically confirmed using enzyme-linked immunosorbent assay. Morphological analyses included light microscope examination of retinal sections and the counting of retinal ganglion cells. Inflammation by infiltration of leukocytes in retina was assessed immunohistochemically. Retinal function was assessed using electroretinography. Results: GDNF expression was confirmed. There was no obvious abnormality in retinal section or increased infiltration by leukocytes after retinal transduction of rAAV-GDNF for 1 year. Counts of retinal ganglion cells were not decreased in rAAV-GDNF–injected eyes. There were no statistical differences in amplitude as well as latency of the electroretinogram-determined a- and b-waves between transduced and untreated eyes. Conclusions: Long-term expression of GDNF within the eyes can be achieved by intravitreal injection of rAAV vectors in the absence of morphological or functional deficits in the retina.