Other recent studies also convincingly showed that a combination of several drugs produced a more potent inhibitory effect on retinal neovascularization than single-drug therapy (67–69). Future treatment of pathologic ocular neovascularization may well rely on combined drug therapy. In this respect, the promising anti-DR agent octreotide may emerge as a key player in such drug combinations.

CONCLUSION

The endogenous peptide SST was isolated from mammalian hypothalamus nearly three decades ago as a potent inhibitory factor of pituitary GH secretion. Now it is appreciated that SST is widely distributed throughout diverse cell types and its actions affect a variety of biological processes such as hormone secretion, neurotransmission, cell proliferation, and angiogenesis. These effects are mediated through five G-protein coupled receptor subtypes, SSTR 1–5. Systemic therapy with the SST peptide analog drug octreotide can result in regression of neovascularization and improve visual acuity in patients with advanced DR. However, the clinical results with octreotide have been variable and have been most favorable for patients receiving high dosage regimens that are well above effective doses required for lowering systemic GH in acromegaly patient. Moreover, the more ischemic the eye, the greater the likelihood of observing a beneficial effect. Therapeutic potential of SST analogs for DR and PDR treatment may be potentially increased if they are used in combination with other anti-angiogenic drugs. The combination therapy may become the mainstream of PDR treatment in the near future.

ACKNOWLEDGEMENTS

A portion of the work described here was supported by the NIH Grant EY015952 to M.B. Grant and G. Shapiro. The authors thank the members of the Grant laboratory for helpful discussion.

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