Ophthalmic Drug Delivery Systems - part 9

Trong một mô hình RGC thoái hóa, khoảng 80% RGCs có thể được cảm ứng phải trải qua quá trình apoptosis và thoái hóa sau transection intraorbital của dây thần kinh thị giác. Một liều duy nhất yếu tố adenovirus não có nguồn gốc từ mã hóa neurotrophic (AdBDNF) coinjected với những kẻ ăn xác thối gốc tự do | 574 Tombran-Tink junctival epithelium are also target tissues into which therapeutic genes can be transferred with recombinant adenovirus. In an RGC model of degeneration approximately 80 of RGCs could be induced to undergo apoptosis and degenerate following intraorbital transection of the optic nerve. A single dose of adenovirus encoding brain-derived neurotrophic factor Ad-BDNF coinjected with a free radical scavenger N-tert-butyl- 2-sulfoph-enyl -nitrone S-PBN resulted in the survival of 63 axotomized RGCs indicating the clinical usefulness of the approach for treating RGCs following optic nerve transection 115 116 . Similar strategies were tested in the management of corneal and conjunctival abnormalities. Adenovirus type 5 Ad 5 vector is reported to successfully deliver the reporter lacZ gene to these tissues in humans and rats. Maximum lacZ expression occurred 2-7 days after inoculation. Moreover the nonspecific upregulation of the inflammatory cytokines IL-6 IL-8 and ICAM-1 in the tissues induced by Ad5 infection was suppressed with betamethasone thereby allowing longer-term transgene expression 117 . Some groups have found that other combinations such as coinjection of E1-deleted AV vectors carrying the lacZ reporter gene with a modified adenovirus encoding a secreted immunomodulatory molecule CTLA4-Ig could significantly reduce the immunological consequences of gene transfer with adenoviruses and thus promote prolonged transgene expression 118 119 . Corneal opacity a condition associated with the expression of TGF-b is another serious cause of visual loss. The accessibility of the cornea has encouraged many in the field to turn to gene therapy alternatives to reduce this condition. An example of the potential usefulness of gene therapy approach for treating corneal opacity is shown in a study that used an adenoviral vector encoding a fusion gene containing the human type II TGF-b receptor and the Fc fragment of human IgG AdTbeta-ExR . Transfection with the

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