Risk factors for capsular phimosis following congenital cataract extraction.

Information processing in the central nervous system relies upon the properties of individual neurons and their arrangement into functional circuits. Alterations in these properties in degenerative conditions thus represent a fundamental challenge for regenerative medicine. As more approaches to restore function at the primary lesion site become available, an important question is the degree to which downstream neural circuits can effectively use reactivated inputs. Vision represents an excellent model system to study this problem. First, the retina and brain perform signal computations to produce a diverse and complex representation of the visual environment (the visual code), which can be assessed using carefully designed stimuli. Second, animal models of photoreceptor degeneration, such as the () mouse, provide well-defined defects in visual input, which have been associated with secondary degeneration and retinal circuit reorganization. Finally, pre-clinical methods of vision restoration are well established. Here, we aim to exploit these advantages and determine the capacity of visual circuits in mice with advanced retinal degeneration to generate an intact visual code. Our approach was to use the optogenetic actuator ReaChR to activate the first post-receptor neurons (ON bipolar cells [OBCs]) in the visual projection of mice, allowing the functional capacity of the surviving retinal circuitry to be probed by measuring ReaChR-driven responses in downstream neurons. Directly photosensitizing OBCs using optogenetics has consistently been shown to restore visual responses in retinally degenerate mice using electrophysiology and behavioral testing. Downstream neurons in treated mice can resolve differences in brightness and rapidly respond to visual stimuli (albeit at higher light levels than wild types [WT]). These are encouraging outcomes but do not address perhaps the most fundamental feature of visual circuits—the ability to parse visual scenes into parallel information pathways with different feature selectivity. The precise content and number of retinal information channels vary with classification method. Baden et al. used two-photon calcium imaging of mouse retinal ganglion cells (RGCs) combined with standardized stimuli designed to test key characteristics—including response polarity, contrast sensitivity, temporal frequency tuning, color opponency, direction selectivity, and receptive field size. Unsupervised clustering of functional responses, combined with cell morphology, revealed 32 output channels. Recently, an equally comprehensive study found as many as 45 RGC types in the mouse retina. This diversity is preserved in the dorsal lateral geniculate nucleus (dLGN), a key retino-recipient brain area in transmitting visual information to the primary visual cortex, where responses reflect the activity of either individual or heterogeneous combinations of different RGC types.