Aberrantly expressed recoverin is functionally associated with G-protein-coupled receptor kinases in cancer cell lines.

Cancer-associated retinopathy (CAR) is an ocular manifestation of a paraneoplastic syndrome whereby immunological reactions toward recoverin (Rec), a retina-specific Ca(2+) binding protein, and its aberrant expression in tumor cells lead to the retinal degeneration. To elucidate functional roles of the aberrantly expression in cancer cells, we performed immunoprecipitation using anti-human Rec mAb. We observed co-precipitation of G-protein-coupled receptor kinases (GRKs) and caveolin-1 with Rec from cell lysates of 293 or SSTW cells. Immunocytochemistry revealed that immunoreactivities toward Rec within the cancer cells were almost identical to those toward GRKs and caveolin-1. The present data strongly suggest that aberrantly expressed Rec should be involved in the GRK-dependent cellular regulation in cancer cells.

Clinical roles of serum autoantibody against neuron-specific enolase in glaucoma patients.

In our recent papers, we found the presence of serum autoantibody against neuron specific enolase (NSE) in some glaucoma patients and suggested that this antibody might have significant roles in pathogenesis of glaucomatous optic neuropathy. In order to evaluate further the clinical roles of serum autoantibody against NSE in glaucoma, serum autoantibody against NSE was examined by western blot analysis and enzyme-linked immunosorbent assay (ELISA) in 4 patients with ocular hypertension (OH) and 242 patients with glaucoma (normal tension glaucoma [NTG], 73 cases; primary open angle glaucoma [POAG], 169 cases), and the relationships between the titers of anti-NSE antibody and clinical characteristics were evaluated. The titers of anti-NSE antibody showed a regular decreasing pattern with deteriorating visual field losses and glaucoma stages in POAG, especially early and late stages. However, no systematic pattern was observed in NTG. Although maximum and mean intraocular pressures (IOP)s and progression of visual field losses showed no correlation with the levels of serum anti-NSE antibody titers in either POAG or NTG, the anti-NSE antibody titers were relatively higher in NTG with visual field deterioration than in those without it. The present observations suggest that serum autoantibody against NSE may be clinically useful for diagnosing early stages of POAG, and for monitoring glaucoma progression of NTG.

Antirecoverin antibody in the aqueous humor of a patient with cancer-associated retinopathy.

PURPOSE: To describe a patient with cancer-associated retinopathy (CAR) in whom antirecoverin antibody was found in the aqueous humor. DESIGN: Interventional case report. METHODS: A 65-year-old man underwent resection of adenocarcinoma of the lung in June 1991 and noted deterioration of vision 10 months later. Goldmann perimetry revealed a ring-like scotoma in each eye, and the electroretinogram was nonrecordable. Aqueous humor and peripheral venous blood were collected for Western blot analysis from this patient and three other patients during surgery for age-related cataract. RESULTS: We found antirecoverin antibody within the aqueous humor and serum in the patient with CAR. In contrast, such imunoreactivities were not observed in specimens from the control patients. CONCLUSION: These observations strongly suggest that antirecoverin antibody penetrates into the aqueous humor and vitreous cavity beyond the blood-retina barrier in CAR.

A high dietary intake of sodium glutamate as flavoring (ajinomoto) causes gross changes in retinal morphology and function.

The purpose of this study was to investigate the effects of glutamate accumulation in vitreous on retinal structure and function, due to a diet high in sodium glutamate. Three different diet groups were created, consisting of rats fed on a regular diet (diet A), a moderate excess of sodium glutamate diet (diet B) and a large excess of sodium glutamate diet (diet C). After 1, 3 and 6 months of the administration of these diets, amino acids concentrations in vitreous were analyzed. In addition, retinal morphology and function by electroretinogram (ERG) of three different diet groups were studied. Significant accumulation of glutamate in vitreous was observed in rats following addition of sodium glutamate to the diet as compared to levels with a regular diet. In the retinal morphology, thickness of retinal neuronal layers was remarkably thinner in rats fed on sodium glutamate diets than in those on a regular diet. TdT-dUTP terminal nick-end labelling (TUNEL) staining revealed significant accumulation of the positive staining cells within the retinal ganglion cell layers in retinas from diets B and C as compared with that from diet A. Similar to this, immunohistochemistry demonstrated increased expression of glial fibrillary acidic protein (GFAP) within the retinal inner layers from diets B and C as compared with diet A. Functionally, ERG responses were reduced in rats fed on a sodium glutamate diets as compared with those on a regular diet. The present study suggests that a diet with excess sodium glutamate over a period of several years may increase glutamate concentrations in vitreous and may cause retinal cell destruction.

[Molecular pathology of retinitis pigmentosa].

BACKGROUND: Retinitis pigmentosa (RP) is primary, chronic, and hereditary chorioretinal degeneration characterized by photopsia, progressive visual loss with ring scotoma, and impairment of dark adaptation. Although modern molecular biology and molecular genetics have identified many causative genes, the molecular pathophysiology of RP is not fully understood, and no effective treatments have been found yet. In recent studies using animal models of RP, new treatments have been devised and their clinical use is being considered. METHOD: In terms of the molecular pathophysiology of RP, we summarized previous studies of genetic impairment of proteins involved in the phototransduction pathway and introduced new possible therapies for RP. RESULTS: We found that most abnormalities of the genes related with the photoxcitation and its inhibition process in the photoreceptor cells caused a variety of clinical manifestations of RP. CONCLUSION: So far, a variety of abnormalities of the genes causing RP have been identified. However, further studies of the relationship between the abnormalities and clinical expression are needed for better understanding of the pathophysiology of RP.

A case of pseudoadenomatous hyperplasia of ciliary body epithelium successfully treated by local resection.

A case of pseudoadenomatous hyperplasia of ciliary body epithelium was reported in which malignant melanoma of ciliary body was suspected. Partial resection for histopathology was performed in conjunction with cataract extraction, anterior resection and photocoagulation. Histopathology of the tumor identified as pseudoadenomatous hyperplasia of ciliary body epithelium. Partial resection of ciliary body tumor may be an alternative method for its differential diagnosis rather than enucleation and iridocyclectomy.

[Effect of tonometry on a glaucoma population study].

PURPOSE: The purpose of this study was to evaluate the influence of tonometry in detecting the occurrence of glaucoma. METHODS: The subjects, 845 out of 3,488 residents aged 40 years or older, were examined according to standard protocols, including tonometry, slit lamp examination, fundus photography, and automatic perimetry as a recall examination. The intraocular pressure in each subject was measured by both Goldmann applanation tonometer(GAT) and noncontact tonometer CT-70 (NCT). RESULTS: The mean +/- standard deviation intraocular pressure measured by GAT was 15.52 +/- 2.57 mmHg, and 15.03 +/- 2.90 mmHg by NCT. There was a statistically significant correlation(p < 0.0001). The difference between pairs of measurements by GAT and NCT was 0.50 +/- 1.93 mmHg. There was no influence of tonometry in detecting the incidence of glaucoma, which was 4.14%; primary open-angle glaucoma 0.59%, normal tension glaucoma 2.6%, primary angle-closure glaucoma 0.47%, and other types of glaucoma 0.48%. The detection of ocular hypertension was different, and was 2.13% with GAT and 2.72% with NCT. CONCLUSION: In our study, the influence of tonometry in detecting the incidence of glaucoma was very small. A noncontact tonometer is considered to be useful for glaucoma population study.

Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist.

PURPOSE: The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology in inherited retinal degeneration, such as retinitis pigmentosa (RP). The purpose of the present study was to evaluate the pharmacologic effects of several Ca(2+) antagonists on the retinal degeneration of RCS rats. METHODS: Several Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine, and nifedipine, were intraperitoneally administered and retinal morphology and functions analyzed. RESULTS: Among the Ca(2+) antagonists, only intraperitoneally administered nilvadipine preserved retinal morphology and electroretinogram responses in RCS rats during the initial stage of retinal degeneration. Studies using immunohistochemistry, RT-PCR, and Western blot analysis revealed significant enhancement of rhodopsin kinase and alphaA-crystallin expression and suppression of caspase 1 and 2 expression in the retina of nilvadipine-treated rats. CONCLUSIONS: These data suggest that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can be used to treat some patients with RP.

Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo.

PURPOSE: In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA). METHODS: Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models. RESULTS: Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa in Western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions. CONCLUSION: These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.

Clinical significance of serum antibody against neuron-specific enolase in glaucoma patients.

PURPOSE: In a recent study, we found the presence of serum autoantibody against neuron-specific enolase (NSE) in glaucoma patients. The purpose of the present paper is to investigate further the clinical significance of the presence of the serum antibody against NSE in glaucoma patients. METHODS: Serum autoantibody against NSE was examined by Western blot analysis in 143 patients with glaucoma (normal tension glaucoma [NTG], 45 cases; primary open angle glaucoma [POAG] 98 cases). Clinical characteristics including visual acuity, visual field, intraocular pressure (IOP), and optic disc features were compared between the serum autoantibody-positive and the serum autoantibody-negative patients. RESULTS: Maximum IOP in the serum anti-NSE antibody-positive patients was significantly lower than that in the negative patients (P <.05). However, no statistical differences were observed in visual field loss, disc cupping, or other clinical factors. During the clinical course, rates of the presence of anti-NSE antibody were significantly higher in the early stages of POAG (P <.0001) with visual field deterioration than without it. Although it was not statistically significant, the positive rates of serum anti-NSE antibody were relatively higher in the later stages of POAG and NTG with visual field deterioration than without it. CONCLUSION: The present observations suggest that the presence of serum autoantibody against NSE may be clinically useful for predicting the progression of visual field loss in POAG patients.

A case of acute angle-closure glaucoma secondary to posterior scleritis in patient with Sturge-Weber syndrome.

BACKGROUND: Sturge-Weber syndrome has been known to be frequently associated with facial cutaneous angioma and ipsilateral glaucoma. However, as far as we know, no cases accompanied by acute angle-closure glaucoma have been reported in patients with Sturge-Weber syndrome. CASE: A 14-year-old boy with unilateral acute angle-closure glaucoma secondary to posterior scleritis associated with Sturge-Weber syndrome is described. OBSERVATIONS: Slit-lamp examination revealed diffuse episcleral venous hemangioma in the right eye. With ultrasound biomicroscopy, a forward shift of the lens-iris diaphragm, a swelling of the ciliary body, and an anterior rotation of the ciliary processes with annular choroidal effusion were detected. The patient responded well to treatment with systemic corticosteroids and cycloplegics. CONCLUSIONS: In our patient, inflammatory changes of the sclera, including swelling of the ciliary body, choroidal effusion, an anterior rotation of the ciliary processes at the scleral spur, and swelling of the lens, leading to closure of the anterior chamber angle, were suggested to be the major mechanisms of intraocular pressure elevation.