Retinal growth factors

RPE plays numerous functions essential for proper structure and function of retinal photoreceptors. They include the maintenance of the blood-retina barrier, selective uptake and transport of nutrients from the blood to the retina and removal of waste products to the blood, enzymatic cleavage of P-carotene into vitamin A, storage of vitamin A and its metabolic transformations, phagocytosis and molecular renewal of POS, expression and secretion of growth factors and immunomodulatory cytokines (Aizman et al., 2007 Aleman et al., 2001 Crane et al., 2000a,b Elner et al., 2006 Holtkamp et al., 2001 Leuenberger et al., 2001 Lindqvist and Andersson, 2002 Maminishkis et al., 2006 Momma et al., 2003 Strauss, 2005). 

Faktorovich, E. G., Steinberg, R. H., Yasumura, D., Matthes, M. and LaVail, M. M. Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Nature 347 83-86,1990. 

Inhibitors of IkBo phosphorylation have been described which irreversibly inhibit cytokine-induced phosphorylation without affecting constitutive phosphorylation. One such compound (Bay 11-7083 ((E)3-[4-f-butylphenyl)-sulfonyl]-2-propenenitrile)) was found to be effective in two animal models of inflammation after intraperitoneal administration [89]. In addition to the effect it has on the expression of adhesion molecules in pro-inflammatory responses, inhibition of the transcription factor NFkB will also have an effect on angiogenesis. Endothelial cells can produce growth factors and cytokines which have pro-angiogenic effects. Some of these factors, e.g. IL-8, TNFa and MCP-1 are known to be produced via NFkB-mediated endothelial cell activation [90,91]. The importance of NFKB-mediated responses in pro-angiogenic endothelium was reflected in studies in which the NFkB inhibitor PDTC decreased retinal neovascularization in the eye of mice [92]. 

Uses Neovascular wet macular degenoation Action Vascular endothelial growth factor inhibitor Dose 0.5 mg intravitreal inj qmo Caution [C ] Hx thromboembohsm Contra Periocular Infxn Disp Inj SE Endophthalmitis, retinal detachment/hemorrhage, cataract, intraocular inflammation, conjunctival hemorrhage, eye pain, floaters EMS None OD Unlikely, but immediate effect would be vision loss and pain d/t t ocular pressure... 

Patel B, Hiscott P, Chatteris D, Mather J, McLeod D, Boulton M 1994 Retinal and preretinal localisation of epidermal growth factor, transforming growth factor alpha, and their receptor in proliferative diabetic retinopathy. Br J Ophthalmol 78 714—718 Pittendrigh CS 1993 Temporal organization reflections of a Darwinian clock-watcher. jAnnu... 

A small number of biopharmaceuticals are delivered by nonparenteral means. Recombinant DNase is given by inhalation aerosol to reduce the viscosity of mucus in the lungs of patients with cystic hbrosis. A platelet-derived growth factor in the form of a gel is administered topically for wound healing. Several hormones and peptides are administered in solution by the intranasal route. A solution of an antisense drug used for the treatment of cytomegalovirus retinitis is injected directly into the eye. 

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL. 1994. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331 1480-1487. 

Takagi, H., King, G. L., Robinson, G. S., Ferrara, N., and Aiello, L. P. 1996. Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells. 

Yang, K., and Cepko, C. L. 1996. Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells. J. Neurosci. 16 6089-6099. 

Suganami, E., Takagi, H., Ohashi, H., Suzuma, K., Suzuma, I., Oh, H., Watanabe, D., Ojima, T., Suganami, T., Fujio, Y., Nakao, K., Ogawa, Y., and Yoshimura, N. 2004. Leptin stimulates ischemia-induced retinal neovascularization possible role of vascular endothelial growth factor expressed in retinal endothelial cells. Diabetes 53 2443-2448. 

Alon T, Hemo I, Itin A, Pe er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995 1 1024-1028. 

AieUo LP, Avery RL,Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994 331 1480. 

Aiello LP, Bursell SE, Clemont A, et al. Vascular endothelial growth factor-induced retinal permeabiUty is mediated by protein kinase C in vivo and suppressed by an oraUy effective beta-isoform-selective inhibitor. Diabetes 1S>97 46 1473. 

BDNF brain derived neurotrophic factor is a member of the nerve growth factor family of trophic factors. In the brain, BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994). 

Durlu, K. Tamai, M. In In Vitro Expression of Epidermal Growth Factor Receptor by Human Retinal Pigment Epithelial Cells in Degenerative Diseases of the Retina, Anderson, R. E., Ed. Plenum Press New York, 1995, pp. 69-76. 

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