Faculty Bibliography

The mechanisms that initiate vitiligo are poorly understood. Vitiligo triggers, such as monobenzone (MB) exposure, induce stress. Understanding the survival responses that combat this stress is key to determining why melanocytes become immune targets. MB induces oxidative and endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR). PERK, a UPR initiator, phosphorylates eIF2alpha and master antioxidant regulator, NRF2. Here, we investigated the impact of PERK-eIF2alpha/-NRF2 activation on sensitivity to MB. Basal phospho-eIF2alpha and NRF2 levels are higher in melanocytes compared to fibroblasts or keratinocytes. PERK downregulation significantly reduced melanocyte viability (implicated in several autoimmune disorders) may link exposure to vitiligoinducing triggers with onset of autoimmunity

Albinism affects about 1 in 4000 people in southern Africa. People with albinism (PWA) face physical, social and psychological challenges including high risk of skin cancer and visual deficits due to ocular hypopigmentation and optic tract maldevelopment. PWA need to avoid the sun, preventing them taking employment that necessitates being outside, while poor vision limits their independence (for example restricting their capacity to drive) and propagates the misconception that PWA have reduced intellectual capacity. Social challenges include negative self-perception, discrimination and more recently a dramatic rise in murders of PWA. While infanticide has long been reported, witchcraft-related killings have sharply increased, especially in Tanzania. Non-governmental organizations such as Under the Same Sun have raised awareness and some efforts have been made by southern African authorities to address the threat. In February 2017, a traditional healer was sentenced to life imprisonment in South Africa for the murder of a PWA whose body was used to make traditional medicine for good luck and increasing wealth. Psychological challenges include delayed mother-affected child bonding, ostracism and difficulty finding marriage partners. Outreach programs, such as those of the Albinism Society of South Africa, play an important role in educating the public, promoting advocacy and social acceptance. Ensuring that PWA are provided with the knowledge and help to face these challenges is thus critical. A valuable education mechanism for PWA is genetic counselling, which has been provided in Johannesburg since the early 1970s. Identification of the genes involved in albinism has made carrier testing and prenatal diagnosis a reality. To date seven prenatal tests have been performed in Johannesburg, with one fetus found to be affected (parents chose not to terminate the pregnancy). Addressing the needs of PWA albinism therefore ranges from countering ancient myths to education about the latest technologies for diagnosis and potential therapies