The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

The retinal ganglion cells (RGCs) are the output cells of the retina into the brain. In mammals, these cells are not able to regenerate their axons after optic nerve injury, leaving the patients with optic neuropathies with permanent visual loss. An effective RGCs-directed therapy could provide a beneficial effect to prevent the progression of the disease. Axonal injury leads to the functional loss of RGCs and subsequently induces neuronal death, and axonal regeneration would be essential to restore the neuronal connectivity, and to reestablish the function of the visual system. The manipulation of several intrinsic and extrinsic factors has been proposed in order to stimulate axonal regeneration and functional repairing of axonal connections in the visual pathway. However, there is a missing point in the process since, until now, there is no therapeutic strategy directed to promote axonal regeneration of RGCs as a therapeutic approach for optic neuropathies.

The retinal Müller glial cells, can enhance the survival and activity of neurons, especially of retinal ganglion cells (RGCs), which are the neurons affected in diseases such as glaucoma, diabetes, and retinal ischemia. It has been demonstrated that Müller glia release neurotrophic factors that support RGC survival, yet many of these factors remain to be elucidated. To define these neurotrophic factors, a quantitative proteomic approach was adopted aiming at identifying neuroprotective proteins. First, the conditioned medium from porcine Müller cells cultured in vitro under three different conditions were isolated and these conditioned media were tested for their capacity to promote survival of primary adult RGCs in culture. Mass spectrometry was used to identify and quantify proteins in the conditioned medium, and osteopontin (SPP1), clusterin (CLU), and basigin (BSG) were selected as candidate neuroprotective factors. SPP1 and BSG significantly enhance RGC survival in vitro, indicating that the survival-promoting activity of the Müller cell secretome is multifactorial, and that SPP1 and BSG contribute to this activity. Thus, the quantitative proteomics strategy identify proteins secreted by Müller glia that are potentially novel neuroprotectants, and it may also serve to identify other bioactive proteins or molecular markers.

The eyes of two whales Balaenoptera physalus and Baleoptera borealis were studied by our group. In this chapter, we present the anatomical, histological, immunohistochemical and ultrastructural studies of the eyes of both types of whales. Based on the results, we can conclude that at least in these two species, the whales are rod monochromat; their resolution is very limited due to the reduced number of retinal ganglion cells, some of which were giant size (more than 100 micrometers in diameter). The excellent representation of melanopsinic positive retinal ganglion cells suggests an adaptation to the dim light as well as involvement in the circadian rhythms. The large cavernous body located in the back of the eye may provide a mechanism that allows them to move the eye forward and backwords; this may facilitate focusing and provide protection from cold deep-sea temperatures.

Osteopontin (OPN) is a secreted glycosylated phosphoprotein that influences cell survival, inflammation, migration, and homeostasis after injury. As the role of OPN in the retina remains unclear, this study issue was addressed by aiming to study how the absence of OPN in knock-out mice affects the retina and the influence of age on these effects. The study focused on retinal ganglion cells (RGCs) and glial cells (astrocytes, Müller cells, and resident microglia) in 3- and 20-month-old mice. The number of RGCs in the retina was quantified and the area occupied by astrocytes was measured. In addition, the morphology of Müller cells and microglia was examined in retinal sections. The deficiency in OPN reduces RGC density by 25.09% at 3 months of age and by 60.37% at 20 months of age. The astrocyte area was also reduced by 51.01% in 3-month-old mice and by 57.84% at 20 months of age, although Müller glia and microglia did not seem to be affected by the lack of OPN. This study demonstrates the influence of OPN on astrocytes and RGCs, whereby the absence of OPN in the retina diminishes the area occupied by astrocytes and produces a secondary reduction in the number of RGCs. Accordingly, OPN could be a target to develop therapies to combat neurodegenerative diseases and astrocytes may represent a key mediator of such effects.