Effects of intraocular or systemic administration of neutralizing antibody against vascular endothelial growth factor on the murine experimental model of retinopathy.

Vascular endothelial growth factor (VEGF), the strongest known angiogenic cytokine and also a potent enhancer of vascular permeability, is closely associated with diabetic ocular complications and other intraocular neovascular diseases. The therapeutic effect of VEGF-neutralizing antibody on oxygen-induced retinopathy in an experimental murine model of proliferative retinopathy was investigated. Intraocular and systemic injection of the antibody resulted in 46% and 18% reductions in the number of nuclei of newly formed vessels of this model, respectively. The results demonstrated that a neutralizing antibody against VEGF was highly effective in the treatment of intraocular neovascularization and suggested possible modes of therapy in human intraocular neovascular diseases, including diabetic proliferative retinopathy.

Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GK rat can be used as a model of initial or latent phase diabetic retinopathy.

Primary ocular and central nervous system malignant lymphoma first manifested as uveitis: possible role of single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine in the diagnostic procedure.

A case of primary ocular and central nervous system malignant lymphoma was reported which was first manifested as bilateral uveitis ten months before the neurological symptoms appeared. The lesion of lymphoma in the central nervous system was clearly demonstrated as a heavy accumulation of N-isopropyl-123I-p-iodoamphetamine by single photon emission computed tomography. Since most brain tumors reportedly show a low uptake of N-isopropyl-123I-p-iodoamphetamine, single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine could be helpful in making the diagnosis, as well as in visualizing primary central nervous system malignant lymphoma.

[Effect of vitronectin on the healing of rabbit corneal epithelial damage].

Vitronectin is one of the major cell-adhesive glycoproteins in mammalian plasma. We investigated the effect of topically applied vitronectin on the healing of rabbit corneal epithelial damage. Vitronectin was purified from rabbit serum by heparin-Sepharose affinity chromatography and autoclaved at 121 degrees C for 20 min after adjusting the concentration to 0.2 mg/ml with saline. Rabbit corneal epithelium was abraded with ethanol and a laser blade in the central portion of the cornea which had been demarcated with a 6.5 mm trephine. Vitronectin eye drops were instilled into the right eye, and sterile saline drops into the left eye as control. The dimensions of the circular epithelial defect were measured at various times after wounding. The area of epithelial damage of vitronectin-treated eyes was smaller than that of control eyes at 2hr-12hr after abrasion (p less than 0.01). These results suggested that topically applied vitronectin might accelerate the corneal epithelial wound healing at an early stage. Vitronectin can be considered as a candidate for treatment of corneal epithelial damage.

[A case of acute tubulo-interstitial nephritis and uveitis syndrome].

We report herein the case of a 14-year-old female who has acute tubulo-interstitial nephritis (AIN) associated with bilateral diffuse uveitis. She was admitted for the evaluation of "proteinuria", following general fatigue and weight loss about 2 weeks ago. Her laboratory data showed mild anemia, hyper gamma-globulinemia, mild proteinuria, and the reduced glomerular filtration rate with the increased urinary excretion of beta 2-microglobulin. The histological examination obtained by renal biopsy showed mild edema and diffuse infiltration of mononuclear cells in interstitium without any glomerular or vascular abnormalities, which were compatible with AIN. As for the etiology of AIN, clinical investigations could not reveal any specific causes, such as bacterial and viral infections, drugs and systemic diseases. About 4 months after the onset of nephritis, she also became to suffer from bilateral diffuse uveitis. Therefore, the diagnosis of the acute tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome) (Vanhaesebrouck et al., 1985) could be confirmed. In her clinical course, it was noteworthy that uveitis relapsed frequently in spite of systemic administration of prednisolone, and it took two years until uveitis cured, whereas the AIN subsided spontaneously prior to the specific treatment. In this case, characteristic findings of granulomatous uveitis was closely similar to those of sarcoidosis, which has been rarely reported in TINU syndrome. In this respect, the involvement of immune processes, especially cell-mediated, was suggested as the possible pathogenesis in this case.

A case report of a patient with retinoblastoma and chromosome 13q deletion: assignment of a new gene (gene for LCP1) on human chromosome 13.

Retinoblastoma (Rb) occurs in hereditary, non-hereditary, and chromosomal deletion forms and the locus for the Rb gene (Rb-1) is closely linked to the locus for esterase D (ESD) assigned to the chromosome 13q14.11. We describe a patient who was predicted to have Rb from the genetic analysis of the chromosome and ESD phenotype. Furthermore, the gene for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1: McKusick catalogue No. 15343, 1983) was assigned to chromosome 13 by deletion mapping. A 3-month-old female had many characteristics of chromosome 13q-syndrome, including dolichocephaly, epicanthus, ptosis, depressed nasal bridge, micrognathia, short webbed neck, and short fifth fingers with clinodactyly and single crease. The karyotype of the patient was 46,XX,del(13) (q14.1-q32), though both the parents had normal karyotypes. As expected, the phenotype of ESD derived from one of the parents, the father in this case, was not detected in peripheral blood lymphocytes by two-dimensional gel electrophoresis (two-DE), indicating that ESD from the father was deleted in the abnormal chromosome 13. The possibility of paternity was calculated to be 0.996 based on the data using 22 genetic markers. Bilateral retinoblastomas could be diagnosed by ophthalmologic examinations before the manifestation of any clinical signs of the tumor and immediately intensive care was taken. In addition, the phenotype of LCP1 derived from the father was not expressed in the lymphocyte proteins from the patient. These data indicate that the gene for LCP1 (LCP1) is located in the region q14.1-q32 of chromosome 13 and may be a useful genetic marker for preclinical diagnosis of Rb.