Survival Factors to Reduce Retinal Degeneration.
One of our current research goals is aimed at developing a medical therapy for these diseases. This effort stems from our initial observation that injecting a peptide (basic fibroblast growth factor or bFGF) into the eye will dramatically reduce the rate of photoreceptor degeneration in an inherited retinal degeneration in the rat, and will reduce light damage in the normal albino rat. Most remarkably, we have found significant survival-promoting activity with several other growth factors, cytokines and neurotrophins, known collectively as "survival factors." Some of these appear to be even more potent than bFGF and may have fewer potentially harmful side effects.

Gene-Based Delivery Methods.
One of the hurdles that must be overcome for survival factors to be used effectively in the human eye is the method of delivery. Because the agents cannot enter the eye via a systemic injection, they must be injected directly into the eye. We are exploring a way to circumvent this problem by using a form of gene therapy to insert genes that will cause cells within the eye to provide survival factors to photoreceptors continuously. Adeno-associated virus (AAV) vectors are used to deliver the survival factor genes.

Gene Augmentation Therapy.
In the case of a retinal degeneration animal model, the RCS rat, we discovered a genetic defect in the Mertk gene that is expressed in the retinal pigment epithelium (RPE) of the eye, but results in photoreceptor cell death. Following this, we successfully reversed the genetic defect by transfer of the normal Mertk gene into the defective RPE cells using viral vectors. Thus, this study demonstrates the power of gene therapy – to reverse the effects of mutant genes in diseases such as retinitis pigmentosa, as well as juvenile and age-related macular degeneration.

Ribozyme Therapy.
Dominantly inherited diseases, such as many forms of retinitis pigmentosa, are characterized by the production of a defective protein that is responsible for photoreceptor cell degeneration. We have found that ribozymes can reduce the amount of defective protein in photoreceptors and thereby extend the life of the cells. The genes for ribozymes are delivered by the use of AAV in the same way as those of growth factor genes and the Mertk gene for gene augmentation studies. In most recent studies, we have found that the ribozymes are effective in preventing photoreceptor cell death not only for a very long time, but also when applied at late stages of the degeneration.

Animal Models of Inherited Retinal Degeneration.
We maintain RCS rats with a naturally occurring, inherited retinal degeneration, as well as congenic RCS rat strains as control animals and with different rates of degeneration. In addition, we have produced 8 lines of transgenic rats with different rhodopsin mutations. These rats have genetic defects similar to those of human retinal degenerations. The animals are an extremely valuable resource, and we ship them to vision scientists worldwide. Please click here for more info.

In sum, our studies offer the possibility of developing pharmacological and gene therapy for some forms of retinal degeneration that may slow their progress or prevent them altogether.