mycophenolic-acid and Retinal-Degeneration

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Feedback, Physiological; Genes, Dominant; Guanosine Monophosphate; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Mycophenolic Acid; Pigment Epithelium of Eye; Protein Conformation; Protein Structure, Tertiary; Purine Nucleotides; Retinal Degeneration; Ribavirin; Ribonucleosides

Sudden acquired retinal degeneration syndrome (SARDS) is a leading cause of irreversible blindness in dogs, yet no treatment has been objectively evaluated, or proven to be effective. Consensus of opinion is that SARDS is immune-mediated, although corticosteroid medications may exacerbate associated systemic signs. We examined the effect of sole-agent treatment with mycophenolate mofetil (MMF), a potent immunosuppressive medication unlikely to exacerbate associated systemic signs.. Ten client-owned dogs with SARDS prospectively recruited within 6 weeks of vision loss.. Clinical history, findings of systemic and ophthalmic examinations, blood parameters, visual navigation ability, electroretinography, and optical coherence tomography (OCT) were collected at baseline and at recheck after approximately 6 weeks of treatment with 10 mg/kg q 12 h of oral MMF.. Twenty percent of dogs (2/10) experienced side effects (diarrhea, vomiting, lethargy), which resolved with reduction in dose to 8 mg/kg q12 h. No significant changes in systemic signs, physical examination findings, or laboratory test results were detected at the recheck examination. Compared with baseline, visual ability significantly declined at the recheck examination, and the amplitude of a slow-onset negative waveform noted on dark-adapted electroretinography was reduced at the recheck examination. The outer retinal layers were significantly thinner at the recheck examination as measured by OCT.. Mycophenolate mofetil as a sole agent has no measureable positive effect on physical health, vision, or retinal structure following a 6-week trial period. Further studies are needed to evaluate other treatment options for SARDS.

Topics: Animals; Dog Diseases; Dogs; Female; Immunosuppressive Agents; Male; Mycophenolic Acid; Pilot Projects; Prospective Studies; Retinal Degeneration; Vision Tests

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) presents with progressive vision loss at 4-7 years of age. Blindness results within 2 years, followed by inexorable neurologic decline and death. There is no treatment or cure. Neuroinflammation is postulated to play a role in the neurodegeneration. The JNCL mouse model demonstrated decreased neuroinflammation and improved motor skills with immunosuppression. Based on this work, a short-term human clinical trial of mycophenolate mofetil has begun, however longer term effects, and whether immunosuppression modulates vision loss, have not been studied. We report a JNCL patient treated with immunosuppressive therapy in whom visual function was comprehensively characterized over 2 years.

Topics: Child; Dark Adaptation; DNA Mutational Analysis; Electroretinography; Female; Humans; Immunosuppressive Agents; Membrane Glycoproteins; Molecular Chaperones; Mycophenolic Acid; Neuronal Ceroid-Lipofuscinoses; Photic Stimulation; Retinal Degeneration; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity