In Silico and In Vivo Study of Lens Regeneration Under theInfluence of Retinoid

Lens regeneration provides a clear example of trans-differentiation of one differentiated cellular type having a distinctive pattern of metabolic activities to another cellular type, which is morphologically and biochemically distinct from the original. An abundant literature exists on lens regeneration in amphibians (Reyer, 1971; Reyer, 1990; Stone, 1959; Yamada, 1967; Jangir et al., 1995). Lens regeneration from non ocular tissue (dorsal iris) has been well documented in amphibians (Reyer, 1954; Reyer, 1977; Eguchi and Itoh, 1982; Eguchi, 1988). However, the capability of iris and retinal pigmented epithelial cells (PECs) to trans-differentiate into lens In vitro is not restricted to urodeles only but is widely conserved in almost all vertebrates, including mammals. Although good lens regeneration from PECs in vivo has been seen in a few species of fishes and urodele amphibians. In cell culture, PECs of almost all vertebrates can switch differentiation to acquire the characteristics of lens (Eguchi, 1997; Okada, 2000). The role of retinoic acid in embryonic and post embryonic development has also been described. (Maden, 2000). It has been found that expression and role of retinoic acid receptor alpha was very important in lens regeneration (Tsonis et al., 2002). Retinoid (vitamin A) are crucial for most forms of life. They have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all-trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. (Rune, 2006) Experimentally, regenerative ability can be activated by using certain chemical likes vitamin A and 3-nitrobenzothiazolo (3, 2-a) quinolinium chloride (NBQ).Scientists has inferred that vitamin A and its derivatives were found to accelerate lens regeneration not only in amphibian frogs but also in mammals like swiss albino mice, rabbit, guinea pigs and pigs (Shekhawat et al., 2001).It has been reported that vitamin A (Retinol) is the immediate precursor to two important active metabolites: Retinal (that is important for vision) and Retinoic acid (which serves as an intracellular messenger that affects transcription of number of genes). Exogenous application of retinoic acid can regulate in a specific manner in the expression of number of homeobox genes implicated in lens regeneration (Maden, 1993). Retinoic acid is lipophilic signaling molecule that is synthesized from ubiquitous non-signaling precursor retinol and functions by activating nuclear receptor that are ligand dependent transcription factors present in responsive cells. The level of retinoic acid in a cell is regulated by cytoplasmic retinoic acid binding protein that may function in intracellular buffers. It has been reported that at molecular level the retinoic acid receptors are members of super family of intracellular hormone receptor which functions as regulator of gene transcription. These receptors comprise two distinct families, the retinoic acid receptor (RAR) family and the Retinoid X receptor (RXR) family; both families have subfamilies which have alpha, beta and gamma receptor proteins (Ralff and Ribeiro, 1995). The Retinoid X alpha receptors are nuclear receptors that mediate the biological effects of retinoid by their involvement in retinoic acid-mediated gene activation.