Alberta Innovates- Health Solutions

Dr. MacDonald's molecular genetic tests confirmed Mr. Krstic's daughter was a carrier for choroideremia, but not affected by it.

Good Fences Make Good Neighbours

The fence that former Edmonton neighbours Mr. Dragan Krstic and Dr. Ian MacDonald built is still sturdy after nearly a decade of Alberta weather, and with a minimum of maintenance it should last another ten years.

If only the same could be said of Mr. Krstic's eyesight. He began to have difficulty with night vision some 30 years ago when he was a young man. The diagnosis sounded innocuous enough: night blindness. But after experiencing gradual decline in daytime vision, he was rediagnosed in 1978 with retinitis pigmentosa, often characterized by night blindness.

By the time Dr. MacDonald moved into the house next door in the early '90s, Mr. Krstic had significant vision loss. Nevertheless, as he puts it, "It wasn't very easily noticed because it was slowly progressive. I grew used to it and could adapt." Even Dr. MacDonald, who became a good friend, and with whom he built a fence between their two properties, did not notice anything wrong.

It was only after Mr. Krstic's youngest daughter started to experience some eye problems and was referred to Dr. MacDonald that a clearer picture emerged of Mr. Krstic's disorder. After discussing the Krstic family's medical history with his neighbour, Dr. MacDonald's suspicions were aroused, and he tested both father and daughter for choroideremia. The results showed Mr. Krstic clearly had the disease. His daughter's eye problems were unrelated to the disease, but her test results identified her as a carrier, who will not, because of the genetics of choroideremia, develop the disease herself.

The mutated gene causing choroideremia is inherited and dominant on the X chromosome. Because males have an X and a Y chromosomes, it most often appears in males whereas females with two X chromosomes inherit one defective X from their father, becoming carriers for the condition. Each one of their offspring have a 50% chance of inheriting the defective X chromosome.

Mr. Krstic emphasizes, "Research is absolutely vital for future therapies for choroideremia and retinitis pigmentosa. We now have the tests which we didn't have before, but it is only with ongoing research that I have hope, not for me, but for my children and their children. I feel fortunate that I have a 'Cadillac' disease in the R.P. group. So many others have 'lemons' and have lost their eyesight at a very young age. At least I've had 50 years."

U of A ophthalmologist Dr. Ian MacDonald's research in choroideremia has earned him international recognition and funding from throughout North America. The retinal degeneration resulting from this rare eye disease, one of the family of disorders known as retinitis pigmentosa (RP), leads progressively to blindness, sometimes by early adulthood. There is no cure, but a diagnostic test developed by Dr. MacDonald can help affected people make necessary changes in their lives.

Dr. MacDonald combined his initial training in molecular applications of clinical genetics with a specialization in ophthalmology after working with a large extended family in Ontario, many of whose members suffered from choroideremia. He came to the U of A in 1992 to help build a centre devoted to eye disease research. His efforts and those of his colleagues in the Ophthalmology Department have led to their laboratory being designated one of the few reference laboratories in North America for choroideremia.

Health Research Fund support gave Dr. MacDonald and his team the means to develop a revolutionary new molecular genetics test for detecting choroideremia. The test gauges antibody reaction to a key protein, extracted from a blood sample, that is implicated in choroideremia. The accuracy and simplicity of the test has attracted international attention.

Dr. MacDonald has also contributed significantly to the Department of Ophthalmology's Alberta family database of rare eye diseases.

Dr. Ian MacDonald is funded through the Health Research Fund, administered by AHFMR on behalf of Alberta Health. He also receives funding from the Medical Research Council of Canada and the RP Foundation Fighting Blindness in Canada.