**5. Conclusion**

have also shown that adult retinal neurons have the capacity to grow on multiple ECM substrates including collagen I, collagen IV, fibronectin and laminin with different affinity. This differential binding influences the degree of branching and elongation of neurites [75].

Matrix components are degraded by extracellular proteolytic enzymes (proteases) acting in the close proximity around the cells after secretion. Many of these proteases belong to two general classes—matrix metalloproteinases (e.g., MMPs and ADAMTSs) and serine proteases (e.g., trypsin, chymotrypsin, elastase) [97–99]. Matrix metalloproteinases represent the largest group with about 50 members identified in vertebrates. Their activity is depended on the

serine proteases, which have a highly reactive serine in their active site. Protease activity is generally confined to the cell surface by specific anchoring proteins, by membrane-associated activators, and by the production of specific protease inhibitors in regions where protease activity is not needed [102]. Their activity is important for the homeostasis and turnover of the

One of the most specialized forms of ECM is the basement membrane, a flexible, tough, and thin sheet of very well-organized components of the ECM. The functions of basement mem‐ branes are to act as platforms for cell adhesion, to provide structural support to a tissue, to divide tissues into compartments, and to regulate cell behavior including polarity. Although small in volume and very thin (typically 40–120 nm), it has a critical role in the architecture of the body [103, 104]. Although the precise composition of the mature basal lamina varies from tissue to tissue and even from region to region in the same lamina, it typically contains the glycoproteins, laminin, type IV collagen and nidogen (also called entactin), along with perlacan [105]. Other common basal lamina components are fibronectin and type XVIII collagen. Interactions of cells with basement membranes are mediated by trans-membrane cell surface receptors, which connect the cytoskeleton of the cell with the extracellular environment,

The mature polarized retina is structurally and functionally supported by two basement membranes that act as boundaries for the neural retina (**Figure 2**). The two basement mem‐ branes are (i) the Bruch's membrane, at the interface of the RPE and the choroid and (ii) the inner limiting membrane (ILM) at the interface of the neural retina formed by the endfeet of Müller cells and the vitreous body [107]. Changes in the organization or composition of these basement membranes lead to various pathologies including diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy or retinal detachment [108–111].

ions [100, 101]. The second group of matrix degrading enzyme is the

Moreover, we demonstrated that much of effects act through integrins activation.

**3. ECM degradation**

or Zn2 <sup>+</sup>

**4. ECM implications in retinal pathologies**

102 Composition and Function of the Extracellular Matrix in the Human Body

leading to the formation of focal adhesions [88, 106].

binding of Ca2 <sup>+</sup>

ECM.

This review aims to provide an overview of the major ECM partners and their functions in the CNS, PNS, and retina. As demonstrated above, ECM is not a passive by-stander present in the inter-cellular space, it actively takes part in controlling the penetration and diffusion of molecules in the extracellular space, sequestration and release of chemokines and growth factors to neurons, area where it should be permissive and inhibitory to specific population of neurons at a specific time. Dysregulation of their synthesis and production in pathological conditions such as spinal cord injury and glaucoma impede the regeneration in both systems. A better understanding of their spatial and temporal expression, molecular assembly and interaction, and production and degradation will be crucial to harness them for encouraging functional recovery in different pathological conditions.
