The eyes have it

Abstract

In his book, ‘The Astonishing Hypothesis’, Francis Crick describes a simple experiment to demonstrate that while both eyes see, the brain interprets information from only one eye at a time. A small mirror is used to direct the gaze of one eye to an uninteresting surface such as a blank wall, while the other eye focuses on a face ahead of the subject. The brain now sees the face, not the wall. By moving a hand transiently across the field of vision of the misdirected eye, the brain’s attention is redirected by the movement towards the wall. The result is that the subject sees a composite image, frequently just a pair of eyes staring out from a blank wall. The effect is very striking, but it also draws attention to the brain’s priorities: the face is dominant over the wall, and movement is dominant over the face. But the fact that the eyes remain even though the rest of the face is erased by the movement across the field of vision, suggests that eyes hold a special place in the brain’s attention. It is perhaps surprising therefore that the genetics of eye pigmentation has attracted less attention than that of skin or hair. In this issue, Rick Sturm and Mats Larsson redress the balance by reviewing the genetic basis for the variations in iris pigmentation. In particular, they highlight an SNP in an intron of a gene upstream from OCA2 that may account for much of the blue/brown eye colour variation by affecting the regulation of OCA2 expression. Eye colour variations reflect the genetic variation affecting genes implicated in the manufacture of the pigment melanin in melanosomes, specialised lysosome-related organelles. Over the years significant progress has been made in understanding both the genetics and the chemistry behind melanin production, yet many key features of melanin remain to be understood, not least the structure of the polymer. In fact, even using the term melanin is a simplification as birds and mammals make two chemically distinct types of melanin, the black/brown eumelanin and the yellow/reddish brown pheomelanin. The review from Sho Ito and John Simon covers the process of ‘mixed’ melanogenesis, reflecting natural systems in which a combination of pheo- and eumelanin is produced and highlights several outstanding questions relating the presence of combinations of different pigment types within the melanosome. One major role for melanosomes in humans is in photo-protection where pigment transferred from melanocytes to keratinocytes affords protection against UV-induced DNA damage. How this is achieved and regulated is an important issue given the alarming increase in incidence of melanoma. One area that is attracting increasing attention is the role of MC1R in photo protection. This receptor signals primarily via the cAMP pathway and is activated in skin in response to keratinocyte-derived MSH. Increased MC1R signalling in melanocytes leads to elevated pigmentation and transcription of genes implicated in melanin synthesis and consequently contributes to the tanning response. Evidence is also accumulating (see Song et al in the next issue of PCMR for example), that MC1R signalling also facilitates repair of DNA damage. One long-time ambition is to induce a natural tanning response and photoprotection without exposure to UV irradiation, and to this end Zalfa Abdel-Malek et al report the use of short MSH-related peptides that can stimulate the MC1R receptor and reduce UV-induced DNA damage in melanocytes. In fact the use of MSH-related compounds for therapeutic purposes is already bringing clinical benefits to patients with specific photo-sensitivities in the form of Alfamelanotide. However, the dangers of unregulated use by the public of compounds such as ‘Melanotan’ to achieve tanning without UV exposure is highlighted in the letter from Veronique de Marmol et al.