REVIEW A shot in the dark: the use of darkness to investigate visual development and as a therapy for amblyopia Clin Exp Optom 2013; 96: 363–372 DOI:10.1111/cxo.12084 Donald E Mitchell PhD MAppSc BSc LOSc Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada E-mail: d.e.mitchell@dal.ca Extended periods of complete darkness have long been used among other early experiential manipulations to explore the role of visual experience in the development of the visual pathways. In the last decade, short periods of darkness have been used to facilitate the imposition of different or conflicting visual input each day to explore the manner by which processes of perinatal development controlled by gene action are refined subsequently by visual experience. Very recently, periods of complete darkness of intermediate length (10 days) have been shown to promote very fast recovery from amblyopia induced by prior monocular deprivation (MD). When imposed immediately after a period of MD, in certain circumstances, darkness appears to insulate against the development of amblyopia. It is proposed that complete darkness may reverse maturation of many of the so-called braking molecules in the visual cortex, so that it reverts to a more juvenile state. Submitted: 12 March 2013 Revised: 16 April 2013 Accepted for publication: 26 April 2013 Key words: amblyopia, darkness, deprivation, stereopsis, visual acuity Vision is the only sense for which its natural physical input can be eliminated completely for extended periods by immersion in a light-free external environment, for which rigorous safeguards are in place to avoid accidental stray light. Although the external environment for other senses can be made stimulus-free, unintended sensory stimula- tion can occur from internal sources. Con- sider audition for example; even with a noise-free environment, unavoidable audi- tory stimulation can still arise through air- borne sound or by bone conduction, as a consequence of self-induced or regular auto- nomic motor responses associated with res- piration or cardiac activity. The ability to eliminate light from the environment permits study of how develop- ment of the visual pathway proceeds after birth in the complete absence of sensory- (visually) driven neural activity. Arguably, this is a similar situation to that prior to birth, when development proceeds on the basis of molecular cues that may be modulated by neural activity of intrinsic origin, such as intrinsic waves of activity in the retina 1,2 but not on the basis of neural activity that is visually driven. The initial developmental papers of Hubel and Wiesel 3 in the 1960s provided the inspiration for many studies directed toward an understanding of the role played by visual experience in postnatal development. In addition to documentation of the functional state of the neonatal cortex, these studies included the many newsworthy demonstrations of the conse- quences of different forms of selected or biased early visual exposure (where the visual input represented an extreme of the normal continuum as with input to just one eye or with input restricted to a single contour orientation, such as horizontal) that were imposed exclusively (that is, provided the only visual input) for extended periods in early life. 4–7 As an aid to the interpretation of studies of the effects of biased early visual exposure, it was necessary to explore the effects of complete visual deprivation. All of these experiments were designed in the context of contemporary views of the state of the neonatal cortex and by the need to inves- tigate potential roles that subsequent visual experience could exert. As a consequence, the periods of selective visual exposure (or deprivation) were exclusive and episodes of normal visual input were specifically avoided. With the advent of new technolo- gies, such as optical imaging of intrinsic signals, 8,9 a consensus has begun to amass on the development of the three major response properties of cells in the primary visual cortex (their specificity for ocular dominance, orientation and direction of motion) and the emergence of the separate columnar maps for these properties onto the cortex. 10 For ocular dominance and orienta- tion selectivity, development appears to occur in two phases, an initial experience- independent stage that is completed at or near birth, followed by a period of plasticity during which neural circuits and cortical maps are refined and subject to alteration by visual experience; 10–13 however, at least in ferrets, 14 directional selectivity may prove an exception to the two-stage viewpoints as this property emerges after birth without an experience-independent stage. The initial studies of visual cortical development imposed periods of darkness or exclusively abnormal visual input that extended for many weeks or months; however, the recognition of a substantial anatomical and physiological scaffold at or near birth suggests that subsequent visual experience may serve more to refine a pre- existing cortical architecture than to sculpt it de novo. Examination of the former role for experience invites different approaches that include the use of mixed daily visual input, in which normal and abnormal visual inputs are pitted against each other on a daily basis. This paper summarises the major findings of studies from my laboratory of the effects of mixed daily visual experience in early post- natal life. Implementation of these studies required the use of a secure darkroom facil- CLINICAL AND EXPERIMENTAL OPTOMETRY © 2013 The Author Clinical and Experimental Optometry 96.4 July 2013 Clinical and Experimental Optometry © 2013 Optometrists Association Australia 363