Sildenafil May Cause Visual Problems in Genetically Predisposed

Dr. Michael Kalloniatis School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia; Centre for Eye Health, Sydney, New South Wales, Australia;MedicalResearch.com Interview with:
Dr. Michael Kalloniatis
School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia; Centre for Eye Health, Sydney, New South Wales, Australia;

Medical Research: What are the main findings of the study? What was most surprising about the results?

Dr. Kalloniatis: Normal mice given a single sildenafil treatment had a transient loss of visual function which recovered in two days. Carrier mice (mice which carry a single copy of a mutation that commonly causes recessive Retintis Pigmentosa) showed a supernormal visual response (a response much larger than the norm) to sildenafil which took two weeks to recover to normal. Carrier mice also showed an increase in an early marker for apoptosis (a protein which suggest cells may be preparing to die) suggesting sildenafil may cause retinal degeneration in these mice.

Medical Research: What should clinicians and patients take away from your report?

Dr. Kalloniatis: Carriers of the mutation tested in this study had a significantly different visual response to sildenafil than normal controls. Thus patients who are carriers for Retinitis Pigmentosa should be aware this family of drugs which use phosphodiesterase inhibitors could potentially cause significant visual changes. However, in the normal population, people who are carriers of recessive genes which cause retinal disease are unlikely to know because they do not have the disease and their vision is normal. The number of people likely to be carriers of a mutation which could cause retinal degeneration is estimated at 1 in 50.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Kalloniatis: We are currently conducting further studies to work out the long term effects of sildenafil on the eyes of carrier mice and the possible biochemical mechanisms behind sildenafil’s actions in the eyes of carrier mice.  Other research that may be important is the effects of multiple sildenafil doses as erectile dysfunction drugs are usually taken regularly and there may be cumulative effects in carriers of recessive Retinitis Pigmentosa.

Citation:
Sildenafil alters retinal function in mouse carriers of Retinitis Pigmentosa
Nivison-Smith L1, Zhu Y1, Whatham A2, Bui BV3, Fletcher EL4, Acosta ML5, Kalloniatis M6.
Exp Eye Res. 2014 Sep 17;128C:43-56. doi: 10.1016/j.exer.2014.08.014.
[Epub ahead of print]