Retinal apoptosis

Seagle, B.L. et al., Melanin photoprotection in the human retinal pigment epithelium and its correlation with light-induced cell apoptosis, Proc. Natl. Acad. Sci. USA, 102, 8978, 2005. 

It has been shown in many studies that protective effects of carotenoids can be observed only at small carotenoid concentrations, whereas at high concentrations carotenoids exert pro-oxidant effects via propagation of free radical damage (Chucair et al., 2007 Lowe et al., 1999 Palozza, 1998, 2001 Young and Lowe, 2001). For example, supplementation of rat retinal photoreceptors with small concentrations of lutein and zeaxanthin reduces apoptosis in photoreceptors, preserves mitochondrial potential, and prevents cytochrome c release from mitochondria subjected to oxidative stress induced by paraquat or hydrogen peroxide (Chucair et al., 2007). However, this protective effect has been observed only at low concentrations of xanthophylls, of 0.14 and 0.17 pM for lutein and zeaxanthin, respectively. Higher concentrations of carotenoids have led to deleterious effects (Chucair et al., 2007). 

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). 

Wenzel, A., Grimm, C., Samardzija, M., Reme, C.E., 2005. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Ret Eye Res. 24, 275-306. 

D1 (10,17S-docosatriene) from DHA using tandem liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry (LC-PDA-ESI-MS-MS)-based lipidomic analysis have been documented in ischemic brain [4] and retinal pigment epithelium [5], This new lipid is called neuroprotectin D1 (1) because of its neuro-protectiveproperties in brain ischemia-reperfusion [4] and in oxidative stress-challenged retinal pigment epithelial cells [5] (2) because of its potent ability to inactivate proapoptotic signaling (see apoptosis, Ch. 35) [5] and (3) because it is the first identified neuroprotective mediator derived from DHA. 

Harris MS, Sakamoto T, Kimura H, He S, Spee C, Gopalakrishna R, Gundimeda U, Yoo JS, Hinton DR, Ryan SJ. (1996). Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells possible involvement of protein kinase C. Curr Eye Res. 15(3) 255-62. 

F. Malchiodi-Albedi, A. Matteucci, G. Formisano, S. Paradisi, G. Carnovale-Scaizo, G. Scorcia, H. Hoerauf, Induction of apoptosis in rat retinal cell cultures by partially fluorinated alkanes. Am. J. Ophthalmol. 139 (2005) 737-739. 

G2. Geromel, V., Kadhom, N., Cebalos-Picot, I., Ouari, O., Polidori, A., Munnich, A., Rotig, A., and Rustin, P, Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring die neurogenic ataxia retinitis pigmentosa (NARP) mutation in file ATPase-6 gene of file mitochondrial... 

Activation of calpain is usually associated with the progression of a necrotic type of cell death (Wang, 2000). However, neuronal necrosis and apoptosis occur in parallel after ischemic injury in vitro and in vivo (Charriaut-Marlangue et al., 1996). Retinal ischemia causes precocious necrosis of neurons in the ganglion cell layer (GCL) and INL, whereas apoptosis appears as the delayed component of neuronal death associated with transient retinal ischemia (Joo et al., 1999). 

Morphological features of apoptosis following retinal ischemia, such as DNA fragmentation, nuclear condensation, and chromatin marginalization have been... 

Daly, F.J. and J.H. Sandell. Inherited retinal degeneration and apoptosis in mutant zebrafish. Anat. Rec. 258 ... 

Joo CK, Choi JS, Ko HW, Park KY, Sohn S, et al. 1999. Necrosis and apoptosis after retinal ischemia Involvement of NMDA-mediated excitotoxicity and p53. Invest Ophthalmol Vis Sci 40 713-720. 

Rosenbaum DM, Rosenbaum PS, Gupta A, Michaelson MD, Hall DH, et al. 1997. Retinal ischemia leads to apoptosis which is ameliorated by aurintricarboxylic acid. Vis Res 37 5445-3451. 

Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, et al. 2000. Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem 275 39625-39630. 

Weishaupt JH, Rohde G, Polking E, Siren AL, Ehrenreich H, et al. 2004. Effect of erythropoietin axotomy-induced apoptosis in rat retinal ganglion cells. Invest Ophthalmol Vis Sci 45 1514-1522. 

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