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Prolonged Tumor Dormancy by Prevention of Neovascularization in the Vitreous¹

Retinal Vascular Service, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 [S. B., D. F., A. P.]; National Cancer Institute, Bethesda, Maryland 20014 [S. B.]; and Department of Surgery, Children's Hospital Medical Center and Harvard Medical School, Boston, Massachusetts 02115 [H. B., J. F.]

Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.

¹ Supported by Grants EY-205 and EY-01368 from the National Eye Institute and CA-14019 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Baltimore Cancer Research Center, 22 S. Greene Street, Baltimore, Md. 21201.

³ Recipient of a Career Award from THE SEEING EYE, Inc.

Received 11/26/75. Accepted 4/26/76.

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