Retinal Function and Morphology in Health, Aging and Disease

Dear Colleagues,

The retina is a complex neural network that lines the posterior part of the eye, with the specific function of transforming the spatiotemporal distribution of light quanta in visual perception. The vision process starts from photoreceptors, which sense and convert the light stimulus into an electric signal by analogically modifying their membrane potentials. This signal is further elaborated by a circuitry of second- and third-order neurons and interneurons cells, mainly analogically; through the optic nerve, it leaves the retina and reaches the brain visual centers where visual perception is ultimately generated.

This process is extremely complex. To ensure the proper transmission and processing of visual information, every single element of the neural network needs to be finely tuned and integrated with the others. For this reason, retinal development is an extensive process during which the neural circuitry uses several steps of remodeling to reach a final perfect organization. Different neurotransmitters, such as acetylcholine, GABA, and glutamate, play a fundamental role in the development of the retina as they modulate connections of transient networks of neurons at different stages. Acetylcholine, in particular, is essential for regulating early developmental events, such as the regulation of the cell cycle and the growth of neurites. Unfortunately, pathological insults and the ageing process can alter retinal organization and severely impair visual processing.

Recently, many advances have occurred in characterizing both the function and structure of the retinal circuitry. Electrophysiological and anatomical data obtained from isolated retinas have been integrated with results obtained in vivo in various animal models and humans, providing better understanding of the complex retinal organization.

Studies on animal models of retinal degeneration have shown that the loss of photoreceptors can generate a series of extensive and regressive changes in the remnant retinal circuitry, which are collectively termed “retinal remodeling”. Bipolar and horizontal cells undergo reactive structural changes, such as dendritic retraction, axonal sprouting, and ectopic synapse formation, which are accompanied by upregulation and downregulation of specific neurotransmitter receptors including type-6 metabotropic glutamate, AMPA, GABA, and glycine receptors. Computational molecular phenotyping of retinas with age-related macular degeneration can detect ectopic neurites of GABAergic amacrine cells and translocation of glycinergic amacrine cells into the outer retinal layers, even in the early stages of the disease before photoreceptors start to degenerate. Ectopic synapses and aberrant neuron processes have also been reported in the retina of aged mice, in which a dysregulation of the LKB1–AMPK pathways within photoreceptors has been linked to age-related synaptic remodeling.

Electrophysiological techniques can be used to non-invasively study functional changes in the retinal circuitry in the setting of specific diseases or ageing. In parallel with a functional assessment, the evaluation of retinal morphological changes, although their onset is known to be delayed compared with functional changes, can offer interesting and relevant information about how dendrites and axons reorganize their structure in response to a retinal injury and how these changes may influence visual information processing. In this context, recently introduced imaging techniques that visualize the retinal structure in vivo can serve as a complementary tool to identify morphological changes in humans or animal models.

This Special Issue of the International Journal of Molecular Sciences entitled “Retinal Function and Morphology in Health, Ageing, and Disease” will focus on recent advances in retinal physiology and pathophysiology of retinal degenerations and aging. Findings from these studies will help to identify targets for new therapeutic products, with the aim of halting or improving the concomitant visual impairment.

Prof. Dr. Silvia Bisti
Guest Editor
Dr. Dario Marangoni
Co-Guest Editor

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• Retinal function
• Retinal degenerations
• Ageing
• Electrophysiology
• Animal models
• Retinal imaging