Unrestricted research funds are used to support several projects relevant to comparative ophthalmology and canine health.  Role: PI

Generation of a Large Animal Stargardt Disease Model. The aim of the project is to generate a dog Abca4 knockout to model Stargardt disease.

Gene Augmentation Therapy to Overcome the Antimorphic Effect of Mutant Crx in the Rdy cat model of Leber Congenital Amaurosis. The major goals are to use rAAV gene therapy to increase expression of normal Crx in the photoreceptors of a dominant cat model of Leber congential amaurosis in order to test the hypothesis that increasing the ratio of wildtype to mutant Crx levels will improve the phenotype. Role: PI  

Cep290-associated Leber Congenital Amaurosis. The major goals are to maintain a CEP290 large-animal colony in preparation for therapeutic gene therapy trials.  Role: PI for MSU portion

Identification of the Genetic Basis of Pigmentary Uveitis in Golden Retrievers. The aim is to identify the genetic basis for pigmentary uveitis in the Golden Retriever breed of dogs. The laboratory will receive blood samples, extract DNA, and prepare it for high-density canine SNP microarray and whole genome sequencing. Role: Co-I.

Demystifying Sudden-Onset Blindness in Dogs. The aim of the project is to further investigate sudden acquired retinal degeneration syndrome in dogs. Role: PI.

Differential Expression and Splice Variant Detection in Ocular Melanosis Affected Cairn Terriers. The aim of the project is to identify differential gene expression in the eyes of dogs that have a bilateral uveal melanocyte proliferation that is a model for inherited pigmentary glaucoma.  Role: PI.

Mapping of and Identification of the Gene Mutation for a Feline Central Retinal Degeneration. The aim of this project is to identify the gene mutation responsible for a feline model of recessive macular degeneration. Role: PI.

Identification of the Genes that Cause Two Types of Retinal Dystrophy in Papillon Dogs. We have identified two unique retinal dystrophies segregating in the Papillon breed of dog. The aim of this project is to complete a GWAS to map the loci and investigate any positional candidate genes. Role: PI.

Intravitreal Allele-specific Anti-sense Oligonucleotides for Reducing Mutant Crx Protein Levels in Large Animal LCA Mode—a Step Towards Restoring Vision in a Dominant Negative Disease. Use of allele-specific antisense oligonucleotides to rescue a large animal Leber Congenital Amaurosis model. Role: PI

Funding for an Ophthalmology Post—Doctoral Scientist. Role: PI

Gene Therapy to Target Retinal Bipolar Cells. The major goals are to perform preliminary AAV gene therapy to rescue the GNB3-/- mouse and rat phenotype. Role: PI

Gene Supplementation Therapy in the RPE65 Deficient Dog. Preclinical assessment of rAAV gene supplementation of the RPE65 deficient dog in support of Phase I/II clinical trials.  Role: PI for all dog studies performed at Michigan State University.