Futoshi Ishikawa

Solid Hyaluronic Acid Film and the Prevention of Postoperative Fibrous Scar Formation in Experimental Animal Eyes

OBJECTIVE To investigate the inhibitory effect of solid hyaluronic acid-carboxymethyl cellulose film (hyaluronic acid film) on the formation of postoperative wound adhesion on rabbit eyes. METHODS We first created a conjunctival flap under which hyaluronic acid film was inserted. Then, we performed trabeculectomy on other rabbit eyes with hyaluronic acid film applied under and above the scleral flaps. Expression of proliferative cell nuclear antigen and alpha-smooth muscle actin (alpha-SMA) were histologically and immunohistochemically examined. RESULTS Hyaluronic acid film significantly prevented adhesions after both kinds of surgery. Particularly, subconjunctival scar formation was significantly inhibited when the film was simply inserted under the wound. Furthermore, the adhesion around the scleral flap of trabeculectomy was less formed in eyes treated with hyaluronic acid film than in control eyes. Immunoreactivity to proliferative cell nuclear antigen almost disappeared after 28 days postoperatively in both treated and control groups. The alpha-SMA-positive cells appeared much less around the film-treated wound than the control eye. CONCLUSION The present results indicate that hyaluronic acid film can inhibit the formation of postoperative adhesion around the conjunctiva and sclera. CLINICAL RELEVANCE The results of this study indicate that this substance has potential benefits for improving ophthalmic surgery, such as filtering surgery for glaucoma.

Ocular blood flow levels and visual prognosis in a patient with nonischemic type central retinal vein occlusion

We look at the case of a 39-year-old female patient suffering from a sudden decrease in her left visual acuity (0.08). Her macular edema was examined using optical coherence tomography, and her optic disc blood flow was examined with laser speckle flowgraphy (LSFG). Additionally, the degree of seriousness of the central vein occlusion was evaluated through fluorescein angiography (FA). Ocular fundus findings revealed central vein occlusion associated with macular edema, and FA determined her disease type as a nonischemic-central vein occlusion. Daily doses of 100 mg of aspirin were administered orally to the patient. Upon administration, her ocular blood flow almost immediately increased. In this study, we demonstrate the potential of LSFG as a means to investigate ocular blood flow.

Misregulation of rhodopsin phosphorylation and dephosphorylation found in P23H rat retinal degeneration

To examine rhodopsin (Rho) functions in P23H rat, kinetics of Rho regeneration and dephosphorylation were investigated by spectrophotometric analysis and immunofluorescence labeling method using specific antibodies toward phosphorylated 334Ser or 338Ser site. Rho dephosphorylation at both sites was extremely delayed in P23H retina as compared to normal ones. Kinetics of Rho regeneration was not altered between normal and P23H rats under dark adaptation. Next, to study the effects of several Ca2+channel blockers on this model, retinal function and morphology were evaluated. Among them, nilvadipine showed a significant protective effect against P23H retinal degeneration. Neurotrophic factor, fibroblast growth factor-2 and Arc, known to suppress the apoptosis in the central nervous system, were significantly upregulated upon administration of nilvadipine. The present study indicates that misregulation of Rho phosphorylation may be involved as an important step in retinal degeneration of P23H and administration of nilvadipine may be a potential therapeutic agent for the retinal degenerations.

A case of idiopathic retinal vasculitis, aneurysm, and neuroretinitis effectively treated by steroid pulse therapy.

represented the final stage of the disease, with absence of both cone and rod responses. According to a genotype– phenotype analysis of the ABCA4 gene, there is an inverse relationship between the presumed residual ABCA4 function and the severity of the disorder, and the ABCA4 gene mutations associated with CRD and RP are similar in this respect. These two cases are consistent with this previous genotype–phenotype analysis. Furthermore, we previously reported that RP resulting from ABCA4 null mutations can exhibit the clinical phenotypes of STGD in the early course of the disease. During childhood, the two patients in this report had been found at another hospital to be suffering from macular degeneration. Although neither ERG nor FA findings were available for the early stage of the disease in either patient, we were able to identify the pathogenesis of these patients by sequence analysis. Therefore, sequence analysis is useful for the diagnosis of panretinal degeneration.

Low expression of rhodopsin kinase in pineal gland in Royal College of Surgeons rat

The Royal College of Surgeons (RCS) rat has been extensively characterized as a model for inherited retinal dystrophy such as retinitis pigmentosa. We have found that significantly low levels of expression of rhodopsin kinase (RK) and aA-crystallin may be involved in the pathogenesis of retinal degeneration in the RCS rat (Invest Ophthalmol Vis Sci. 1999,40:2788-2794). In the present study, we examined the expression of photoreceptor specific proteins in the pineal gland (PG) including rhodopsin kinase (RK), arrestin and recoverin, which are known to be commonly present in both photoreceptor and PG, in order to elucidate the pathological relationship between retina and PG during retinal degeneration. Among these proteins, RK expression was significantly decreased with advancing age (3–5 weeks old) in RCS rat. However, in contrast, arrestin expression in RCS PG was comparable with control PG and no expressions of recoverin and other G-protein coupled receptor kinases (GRKs 2, 5 and 6) were detected in RCS PG during 3–5 weeks of age. By administration of nilvadipine, an effective Ca 2+ antagonist that was shown to preserve RCS retinal degeneration, RK expression was significantly enhanced.

Changes in Intraocular Indocyanine Green Concentrations during Macular Hole Surgery

Purpose: To report changes in intraocular indocyanine green (ICG) concentration which was used for visualization of the internal limiting membrane (ILM) during vitreous surgery on 3 eyes of 3 patients with full-thickness macular hole. Methods: During intraocular surgery with ICG-assisted ILM peeling, aliquots of intraocular fluid obtained at 1 min after ICG administration (0.5 ml of 5 mg/ml ICG solution), before and after ILM peeling, and before and after fluid/gas exchange were subjected to spectrophotometric analysis. Results: Intravitreous concentrations of ICG were dramatically reduced to approximately 0.4 µg/ml during the surgery for macular hole in all cases. Conclusion: The present study indicates that the levels of remaining intraocular ICG concentrations after macular hole surgery are much lower than the levels that induced retinal toxicity in experimental models.

Effects of calcium channel blockers on retinal morphology and function of rd mouse

Retinitis pigmentosa (RP) is a disease of inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been available for RP. Several animal models with inherited retinal degeneration have been studied in order to elucidate the molecular pathology of RP, and to design an effective therapy for it. Frasson et al. [1] recently reported rod photoreceptor rescue by d-cis-diltiazem, a Ca2+ channel blocker in a different animal model of RP, rd mouse, in which the gene encoding cyclic guanosine monophosphate phosphodiesterase is affected. In addition, our group found that systemic administration of another type of Ca2+ channel blocker, nilvadipine, caused significant preservation of retinal morphology and function in Royal College of Surgeons (RCS) retinal degeneration [2]. These data suggest that the regulation of intracellular Ca2+ levels may be a possible therapy to prevent progressive retinal degeneration in RP and its animal models. So far, many Ca2+ channel blockers have been used in our clinical practice. Therefore, it seems very important to know which Ca2+ channel blocker is the most effective for retinal degeneration in RP.

Pharmacological Aspects of Nilvadipine-Induced Preservation of Retinal Degeneration in RCS Rat Analyzed by mRNA Profiling Assay

In our study, we found that the Ca2+ antagonist nilvadipine was beneficial for the preservation of photoreceptor cells in The Royal College of Surgeons (RCS) rats. Here, in order to elucidate mechanisms of its nilvadipine-induced photoreceptor preservation, we analyzed altered gene expressions of the retina in RCS rats administered nilvadipine by mRNA profiling assay. Total RNA isolated from the retina with or without nilvadipine was converted into cDNA. Utilizing DNA microarray analysis methods, we compared the overall expression patterns for 1101 genes that were commonly expressed in rodent. Of the total genes, the expression of less than 30 genes was altered significantly including that of several genes involved in cellular regulation. On the basis of these data, it is suggested that microarray analysis is a useful tool and applicable for studying the pharmacological effects of several drugs including Ca2+ channel blockers to retinal degeneration.

Nilvadipine, a Ca2+ Antagonist, Effectively Preserves Photoreceptor Functions in Royal College of Surgeons Rat

The Royal College of Surgeons (RCS) rat is the most extensively studied animal model for understanding the molecular pathology of inherited retinal degeneration, such as retinitis pigmentosa (RP). We recently found lower levels of rhodopsin kinase expression in RCS rats as compared with control rats, leading us to speculate that misregulation of the phototransduction pathways by the low levels of rhodopsin phosphorylation might be a critical step causing the retinal degeneration. Here, effects of suppression of recoverin-dependent inhibition of rhodopsin phosphorylation on the retinal degeneration in RCS rats by lowering intracellular Ca2+ levels by intraperitoneal administration of nilvadipine, a calcium antagonist, and retinal functions and morphology were analyzed. We found that systemic administration of nilvadipine caused remarkable preservation of photoreceptor functions, electroretinogram responses, and retinal morphology in RCS rats during the initial stage of the retinal degeneration. On the basis of these data, it was strongly suggested that nilvadipine is beneficial for the preservation of photoreceptor cells in RCS rats and can potentially be used to treat some RP patients.

Cancer-Associated Retinopathy (CAR) is Effectively Treated by Ca2+ Antagonist Administration

Cancer-associated retinopathy (CAR) is a paraneoplastic ocular manifestation in which recoverin acts as an autoantigen recognized by sera from patients. Recently, we have found that CAR-like retinal dysfunction was produced by intravitreous administration of antirecoverin antibody in Lewis rat eyes. In the present study, nilvadipine, a Ca2+ antagonist recently found effective as a drug for inherited retinal degeneration, was evaluated for its effectiveness on the retinal degenerations in CAR using these models. Under medication with nilvadipine, the functional and morphological properties of the retinas were evaluated functionally and morphologically following antirecoverin antibody intravitreous injection into Lewis rats’ eyes (six rats, 12 eyes in each experimental condition were used). Administration of nilvadipine to the antirecoverin antibody-treated rats caused significant improvement of the deterioration of ERG and normalization of rhodopsin phosphorylation. The present data indicated that antirecoverin antibody-induced retinal dysfunction can be effectively treated by systemic administration of nilvadipine.