Effect of Intravitreal Administration of Indomethacin on Experimental Subretinal Neovascularization in the Subhuman Primate

Sakamoto, Takako; Soriano, Danilo Sone; Nassaralla, João Jorge; Murphy, Todd L.; Oganesian, Arutun; Spee, Christine; Hinton, David R.; Ryan, S.J.

doi:10.1097/00006982-199616020-00032

Cited by 11 publications

(17 citation statements)

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“…The angiographic interpretation was confirmed by microscopic evaluation. SRN has been produced in rabbits by subretinal implants of basic fibroblast growth factor-containing microspheres (10) and in monkeys (11) and mice (38) in response to argon laser photocoagulation. Although these represent useful techniques for studying angiogenesis, it is not possible to determine whether chemically and traumatically induced neovascularization utilizes the same molecular mechanisms that occur in human ARMD and SRN.…”

Section: Discussionmentioning

confidence: 99%

The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

Smith¹,

John²,

Zabeleta³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst͞؉ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst͞؉ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents.

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Section: Discussionmentioning

confidence: 99%

The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

Smith¹,

John²,

Zabeleta³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…In diabetic dogs, sulindac decreased retinal capillary basement membrane thickening and diabetic retinopathy (Gardiner et al 2003). In nonhuman primates, continuous infusion of indomethacin into the vitreous cavity reduced vascular leakage (Sakamoto et al 1995). Topically applied indomethacin reduced uveitis in rabbits (Yamauchi et al 1979) and markedly inhibited the breakdown of the blood aqueous barrier after paracentesis or argon-laser photocoagulation of the iris in rabbits (van Delft et al 1987).…”

Section: Effects Of Cox Inhibitors On the Eyementioning

confidence: 99%

“…Topically applied ns-NSAIDs (e.g., diclofenac, flurbiprofen, ketorolac, suprofen, indomethacin) inhibit COX-1 and COX-2 and are used in the management of various ophthalmic conditions such as seasonal allergic conjunctivitis; photophobia and pain after corneal refractive surgery; postoperative inflammation after cataract surgery; postoperative topical analgesia; prevention and treatment of cystoid macular edema; and prophylaxis of surgical miosis (Frucht and Zauberman 1984;Gaynes and Fiscella 2002;Sakamoto et al 1995;Schalnus et al 2003;Takahashi et al 2003). In veterinary medicine, systemic ns-NSAIDs (e.g., carprofen and flunixin meglumine) are used to treat uveal conditions (Giuliano 2004).…”

Section: Effects Of Cox Inhibitors On the Eyementioning

confidence: 99%

Pathophysiology of Cyclooxygenase Inhibition in Animal Models

Radi

2009

Toxicol Pathol

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Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandins (PGs), which play a significant role in health and disease in the gastrointestinal tract (GI) and in the renal, skeletal, and ocular systems. COX-1 is constitutively expressed and found in most normal tissues, whereas COX-2 can be expressed at low levels in normal tissues and is highly induced by pro-inflammatory mediators. Inhibitors of COX activity include: (1) conventional nonselective, nonsteroidal anti-inflammatory drugs (ns-NSAIDs) and (2) COX-2 selective nonsteroidal antiinflammatory drugs (COX-2 s-NSAIDs). Inhibition of COX-1 often elicits GI toxicity in animals and humans. Therefore, COX-2 s-NSAIDs were developed to provide a selective COX-2 agent, while minimizing the attendant COX-1-mediated GI toxicities. Rats and dogs overpredict COX inhibition for renal effects such as renal handling of electrolytes in humans. COX inhibitors are shown to have both beneficial and detrimental effects, such as on healing of ligament or tendon tears, on the skeletal system in animal models. Certain ophthalmic conditions such as glaucoma and keratitis are associated with increased COX-2 expression, suggesting a potential role in their pathophysiology.

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“…It also may prevent recurrence following laser treatment and possibly be used as a prophylaxis (8). There are a variety of candidate drugs under consideration including matrix metalloproteinase inhibitors, VEGF inhibitors, TNP-470, interferon alpha, indomethacin, tranilast, kinase inhibitors, thalidomide, and others (8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Preventive Versus Treatment Effect of Ag3340, a Potent Matrix Metalloproteinase Inhibitor in a Rat Model of Choroidal Neovascularization

Bradey

Cheng

Bartsch

et al. 2004

Journal of Ocular Pharmacology and Therapeutics

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Purpose: AG3340 (prinomastat) is a nonpeptidic, small-molecular-weight, synthetic matrix metalloproteinase inhibitor (MMPI) with selective inhibitory action of MMP-2, MMP-9, MMP-3, and MT-MMP1. We evaluated AG3340 injected intravitreally to treat choroidal neovascularization in a laser induced rat CNV model. Methods: In the pretreatment group, the drug was injected the same day after induction of choroidal neovascularization by diode laser. In the treatment group, the drug was injected 2 weeks after induction of choroidal neovascularization (CNV). Fluorescein and indocyanine green angiography were performed to evaluate CNV. ERG recordings and histology were performed to assess toxicity and the CNV lesions. Results: When used at the time of CNV induction, 62.8% of lesions in control versus 22.8% of the laser lesions in treated eyes developed CNV (p < 0.0001). The invading fibrovascular complex was thicker in the control eyes than that in the treated eyes. No signs of toxicity were detected. When used to treat established CNV, the percentage of leakage in treated and control eyes were 54.1% and 58.9% respectively (p > 0.05). Prinomastat was effective when given at the time of induction of CNV in the rat model. Administration of prinomastat 2 weeks after laser induction did not show efficacy. Conclusion: Prinomastat was active in the earliest stages of experimental CNV. It might be best used in combination with photodynamic therapy to inhibit recurrence of CNV from temporarily closed new vessels.

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Effect of Intravitreal Administration of Indomethacin on Experimental Subretinal Neovascularization in the Subhuman Primate

Abstract: Objective: To examine the effect of indomethacin, a cyclooxygenase (CO) inhibitor, on laser-induced subretinal neovascularization (SRN)

Cited by 11 publications

References 0 publications

The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

Pathophysiology of Cyclooxygenase Inhibition in Animal Models

Preventive Versus Treatment Effect of Ag3340, a Potent Matrix Metalloproteinase Inhibitor in a Rat Model of Choroidal Neovascularization

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