Antioxidant Therapy Prevents Vision Loss in Rare Birth Defect

The paper — published Jan. 19 in Scientific Reports — describes the combination therapy that resulted in preventing the retinal degeneration that occurs in an animal model of Smith-Lemli-Opitz syndrome (SLOS).

Caused by the body’s inability to make cholesterol, SLOS is a birth defect that results in multiple neurosensory and cognitive abnormalities, physical deformities and disabilities, including impaired vision. In severe cases, it can be fatal.

“Using our combination therapy approach, we were able to prevent otherwise progressive and irreversible retinal degeneration from occurring in a rodent model of this hereditary human metabolic disease that we had previously developed,” says Steven J. Fliesler, PhD, the paper’s lead author and UB Distinguished Professor and Meyer H. Riwchun Endowed Chair Professor of ophthalmology.

To treat the condition, dietary supplementation with cholesterol is prescribed in addition to treating the individual conditions seen in babies with SLOS, ranging from those affecting the central nervous system (including the eyes) to the heart, lungs, gastrointestinal tract and genitourinary systems, as well as the musculoskeletal system.

However, Fliesler notes that outcomes from the supplementation vary widely.

“We hypothesized — based upon findings in the literature, including seminal work from my lab — that oxidation of a specific molecule (which happens to be the immediate precursor of cholesterol) was key to the disease mechanism,” he explains.

“We reasoned that blocking such oxidation with antioxidants should prevent or significantly reduce the severity of the retinal degeneration observed in the rodent model. That evidence-based therapeutic approach worked.”

Fliesler cautions that more studies are needed before scientists may be able to suggest a similar type of combination therapy might also be effective with humans.

“It is advisable to conduct additional preclinical studies using appropriate animal models of the disease — such as those we used in this study — in order to refine dosages and specific antioxidant combinations,” he says. “Some emerging, highly potent antioxidants not yet approved for human use might in the future be appropriate to investigate as a potential treatment for human SLOS patients.”

Fliesler is vice-chair and director of research for the Department of Ophthalmology and director of research for the Ira G. Ross Eye Institute Vision Research Center. Additionally, he is a Research Career Scientist at the VA Western NY Healthcare System, where he directs the Ross Eye Institute Vision Research Center.

Co-authors on the study from the Jacobs School are:

• Sriganesh Ramachandra Rao, a doctoral candidate in the Department of Biochemistry
• Nadav I. Weinstock, an MD/PhD candidate in the Hunter James Kelly Research Institute

Additional co-authors are from the following institutions:

• Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
• Cleveland Clinic Cole Eye Institute 
• Louis Stokes Cleveland VA Medical Center
• University of Washington School of Pharmacy

The research was supported by:

• Clinical and Translational Science Award to UB from the National Center for Advancing Translational Sciences
• Department of Veterans Affairs
• Fight for Sight
• National Institutes of Health/National Eye Institute
• Research to Prevent Blindness