Retinal formation

FIGURE 17 11 Imine formation between the aldehyde function of 11 as retinal and an ammo group of a protein (opsin) is involved in the chemistry of vision The numbering scheme in retinal is specifically developed for carotenes and related compounds... 

The incidence and severity of ROP both rise with decreasing birthweight and gestational age. Fielder et al. (1992) have shown that the incidence of ROP in infents of < 1700 g birthweight is about 50%, although only 5% had severe disease. Severe ROP results in vitreous haemorrhage from new vessel formation on the immature retina, retinal traction and eventually retinal detachment (Fig. 9.6). In the most severe cases, retinal detachment is complete, resulting in total blindness. Treatment with cryotherapy or laser has halved the incidence of retinal detachment. 

Aminoguanidine has been shown to prevent the formation of AGEs (Brownlee et al., 1986) and treatment with this drug prevents retinal pericyte loss in STZ-induced diabetic rats (Hammes et al., 1990). More recendy, functional and structural impairments in peripheral nerves are ameliorated by aminoguanidine in male Wistar rats (Yagihashi et al., 1992). These data surest that inhibitors of non-enzymatic glycosyiation may have a future role in the treatment of diabetic complications. 

Adhikari, S., Kapoor, S., Chattopadhyay, S., and Mukheijee, T. 2000. Pulse radiolytic oxidation of P-carotene with halogenated alkylperoxyl radicals in a quaternary microemulsion Formation of retinal. Biophys. Chem. 88 111-117. 

Anderson, DH, Ozaki, S, Nealon, M, Neitz, J, Mullins, RF, Hageman, GS, and Johnson, LV, 2001. Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium implications for the process of drusen formation. Am J Ophthalmol 131, 767-781. 

Sundelin, SP and Nilsson, SE, 2001. Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants. Free Radio Biol Med 31, 217-225. 

Lampert, J. M., J. Holzschuh et al. (2003). Provitamin A conversion to retinal via the beta,beta-carotene-15,15 -oxygenase (bcox) is essential for pattern formation and differentiation during zebrafish embryogenesis. Development 130(10) 2173-2186. 

Nagao, A. and J. A. Olson. 1994. Enzymatic formation of 9-cis, 13-cis, and all-fraras retinals from isomers of beta-carotene. Faseb J 8(12) 968-973. 

Vitamin A (retinol) is not a classic antioxidant although it is frequently related to a group of antioxidant vitamins E, C, and A. Murata and Kawanishi [83] found that retinol and its derivative retinal induced the formation of 8-HOdG in HL-60 cells. This process was supposedly mediated by hydroxyl radicals formed from hydrogen peroxide (the product of superoxide dismutation) and endogenous transition metal ions. 

The above findings are supported in the other studies of the inhibitory effects of flavonoids on iron-stimulated lipid peroxidation. Quercetin was found to be an inhibitor of iron-stimulated hepatic microsomal lipid peroxidation (/50 = 200 pmol I ) [134]. Flavonoids eriodictyol, luteolin, quercetin, and taxifolin inhibited ascorbate and ferrous ion-stimulated MDA formation and oxidative stress (measured by fluorescence of 2,7,-dichlorodihydro-fluorescein) in cultured retinal cells [135]. It should be mentioned that in recent work Heijnen et al. [136] revised the structure activity relationship for the protective effects of flavonoids against lipid peroxidation. 

The active compound within the bacillary layer is retinal. To simplify the photo-physics within the rods and cones hugely, absorption of a photon initiates a series of conformational changes that lead ultimately to photo-isomerization of retinal from the 11-cis isomer to the 11-trans isomer see Figure 9.20. The uncoiling of the molecule following photo-excitation triggers a neural impulse, which is detected and deconvoluted by the brain. The photochemical reaction is breakage and, after rotation, re-formation of the C=C bond. 

Blatz and Mohler38 have performed 2D NOE NMR experiments on the protonated f-butylamine Schiff base of all-fraws-retinal using different counterions, each carrying at least one nonexchangeable proton. The study has indicated that a proton on the counterion molecule is spatially close, in aprotic solvents, to the protons of the chromophore near the positively charged nitrogen. It has also shown that the ion-pair formation is relaxed in either the presence of excess carboxylic acid (the counterion) or when using methanol as a solvent. 

Experiments were performed at 5°C in order to arrest the cis-trans isomerization of the protonated Schiff base. Spectra with one equivalent of acid and different mixing times showed one NOE cross-peak between H15 of the retinal molecule and the proton on the counterion, as shown for a mixing time of 0.4 s in Figure 10. The strong chemical shift dependence of the H15 resonance on the concentration of the acid dictated the use of less than one equivalent of the protonating formic acid, and therefore an incomplete protonation (>80%) of the retinal, in order to avoid an overlap between the formate and the H15 peaks in the spectrum. This should not affect the observed result since an average chemical shift, between those of HI 5 of the retinal in its nonprotonated and protonated... 

Using two-dimensional NMR spectroscopy, the spatial location of various carboxylate anions relative to the polyene chain of the protonated Schiff base of all-fraws-retinal was determined. The observed intermolecular NOE cross-peaks between a proton on the counterion and a proton near the nitrogen atom indicate the existence of ion-pair formation between the protonated retinal Schiff base and various counterions in chloroform. The results suggest that the most likely site of the carboxylate group of the counterion is in the immediate vicinity of the positively charged nitrogen atom of the retinal Schiff base. 

---