Deficiency of the enzyme HGSNAT leads to Sanfilippo type C, one of the rarer subtypes of Sanfilippo syndrome. Some patients with Sanfilippo type C show signs of vision loss, though the effect of the disease on the eye is not fully understood.
A recently published study by researchers in Canada and the USA, led by Prof. Alexey Pshezhetsky, has investigated the effects of Sanfilippo on the retina—the layer of light-sensing cells at the back of the eye. For their study, the team examined the eyes of 6-month-old type C mice that produce no HGSNAT protein. They also studied a Sanfilippo type C human eye from a 35-year-old deceased donor with family consent.
Two important types of retinal cells, the rods and cones, were analysed in the study.
Rod cells are most active when there is little light, and they help to see in grayscale. In the Sanfilippo type C mouse model, the team recorded an almost 50% decrease in rod cells in the retina compared to the mice without Sanfilippo, and their findings indicated severe rod degeneration.
Cone cells help to see colour and are active during higher light levels like at day time. They also help to differentiate between two close objects. No change in the numbers of cone cells was observed in the mice at six months of age between the mice with and without Sanfilippo type C.
The eye from a deceased donor with Sanfilippo type C was compared with another eye from an age-, sex-, and race-matched donor. The eye size of the donor with Sanfilippo was noticeably smaller than the healthy donor, and when examined under a microscope, the retina was thinner and had fewer cells.
The findings from both the mouse model and donated eye indicate that severe retinal degeneration is found in Sanfilippo type C.
Six-month-old mice were specifically chosen for the study as the mouse eye has fully developed by this time point, but the behavioural symptoms of the disease have not emerged. The team suggests that retinal degeneration may also start early in the disease in patients.
This study represents the first to look at eye symptoms in mice with Sanfilippo type C that produce no HGSNAT protein. Further studies are needed to characterise vision loss in Sanfilippo type C, including when vision loss starts and how it progresses. The mouse model of Sanfilippo type C used in the study could be a valuable model to explore vision loss in the disease.
Severe retinal degeneration has also been seen in mouse models of Sanfilippo type A and type B. Another study, led by Professor Kim Hemsley from Flinders University, found that the progressive retinal disease in Sanfilippo type A mice mirrors the rate of brain degeneration.
Together these findings suggest that retina degeneration could be used to help with early diagnosis, to track disease progression, or to evaluate the effectiveness of potential treatments.