Retinal cell differentiation

BRGl BRGl Zebrafish Not known Retinal cell differentiation [274]. 

Gregg, R.G., Wilier, G.B., Fadool, J.M., Dowling, J.E., and Link, B.A. (2003) Positional cloning of the young mutation identifles an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation. Proc. Natl. Acad. Sci. USA 100, 6535-6540. 

Guimaraes MZ, Hokoc JN, Duvoisin R, Reis RA, De Mello FG (2001) Dopaminergic retinal cell differentiation in culture modulation by forskolin and dopamine. Eur J Neurosci 75 1931-1937. 

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Chemistry. The commercial form cf vitamin A is all-trans retinol, usually formulated as the acetate or palmitate ester. The active forms are the two oxidation products (Fig. 8.1, (l)retinal, which is a structural component of the visual pigment rhodopsin, and (2)retinoic acid, which is required for cell differentiation. There are specific nuclear receptors for retinoic acid. Although the vitamin is marketed in the all-trans form, retinal and retinoic acid are present, in vivo in cis forms. There are also commercial forms related to the retinoic acid structure that have cis stereochemistry. 

Two retinoids, retinoic acid and retinal, appear to have most of the biochemical functions attributed to vitamin A Retinoic acid is required for cell differentiation and is the ligand for two families of nuclear receptors, RAR . y and RXR 0 y. These receptors are part of a family of superreceptors that include the steroid hormones and cholecalciferol. Vitamin A deficiency can lead to a variety of symptoms depending on the age of the deficient person. The most serious syndrome is keratomalacia, which results in desiccation, ulceration, and xerophthalmia of the cornea and conjunctiva. It is one of the leading causes of blindness in infants and children. 

Glutamate s role as a neurotransmitter in the vertebrate retina is reviewed by Barnstable (1993), Brandstatter et al. (1998) and Lo et al. (1998). As the cell bodies of different retinal cell types are in different laminae (Fig. 10), we can assign which general cell types express which glutamate receptor subunits. However, there are different subsets of the same cell class, e.g., there are at least 10 different types of on- and off-bipolars, and multiple subtypes of the other cell classes (Stevens, 1998). Without cell-type markers and double-labelling studies, ISH can not differentiate these. The cones and rods release glutamate onto the bipolar cells only off-bipolars use ionotropic receptors at this synapse on-bipolars use the metabotropic receptor mGluR6 instead. The distribution of NMDA and non-NMDA receptor mRNAs in the retina is summarized in Fig. 10. 

The function of certain carotenoids as provitamins A (retinol (13), 3,4-didehydroretinol (14) and retinal (18)), treated in the previous section, is during the last two decades further expanded as precursor role for additional biologically important retinoids, namely the all-trans and 9-cis isomers of retinoic acid (19), Fig. 6. Their function in growth regulation, development and cell differentiation via specific nuclear receptors are being clarified [24,31], The origin of all-trans and 9-cis retinoic acid (19) has been considered [29,32,33],... 

Finally, other reported functions of NT-4/5 include the induction of granular cell differentiation at late stages of cerebellar development (Gao et al., 1995a), and the promotion of survival and neurite outgrowth of retinal ganglion neurons in cultured explants from adult rats (Cohen et al., 1994). 

Directed differentiation towards retinal lineages has also been investigated for application in cell-based therapies to treat retinopathies and degenerative disorders such as age-related macular dystrophy. The production of retinal cells has recently been reported from ESCs and induced pluripotent stem cells with a cocktail of small molecules in serum-free conditions an ALK inhibitor, a Rho kinase inhibitor and a casein kinase inhibitor. ... 

Retinoic acid (Dl) is formed irreversibly from retinaldehyde (Futterman, 1962) and therefore is not a precursor for rhodopsin. Retinoic acid supports growth, promotes epithelial cell differentiation, and suppresses neoplastic development (e.g., Zile et al., 1979 Roberts and Frolik, 1979 Lotan, 1980). It occurs in the retina (Saari et al., 1982), but it is not known whether it has a speciflc retinal function. 

We have already encountered the protein rhodopsin, the photoreceptor that generates and transmits nerve impulses in retinal cells (Real Life 18-2). Other proteins serve for transport and storage. Thus, hemoglobin carries oxygen iron is transported in the blood by transferrin and stored in the liver by ferritin. Proteins play a crucial role in coordinated motion, such as muscle contraction. They give mechanical support to skin and bone they are the antibodies responsible for our immune protection and they control growth and differentiation—that is, which part of the information stored in DNA is to be used at any given time. 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

Dunn, KC, Aotaki-Keen, AE, Putkey, FR, and Hjelmeland, LM, 1996. ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res 62, 155-169. 

Momma, Y, Nagineni, CN, Chin, MS, Srinivasan, K, Detrick, B, and Hooks, JJ, 2003. Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus. Invest Ophthalmol... 

K. Hosoya, M. Tomi, S. Ohtsuki, H. Takanaga, M. Ueda, N. Yanai, M. Obinata, and T. Terasaki. Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a transgenic rat. Exp. Eye Res. 72 163-172 (2001). 

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