Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 73 records · Page 4Linked to original sources

PubMed2005

Early visual results with the 1CU accommodating intraocular lens.

PURPOSE: To prospectively assess the clinical outcome after implantation of the 1CU accommodating intraocular lens (IOL) and a foldable acrylic IOL (AcrySof, Alcon). SETTING: Department of Ophthalmology, Tokyo Dental College, Ichikawa Hospital, Ichikawa, and Minami Aoyama Eye Clinics, Tokyo, Yokohama, Japan. METHODS: Twenty-two eyes of 16 patients with cataract had phacoemulsification implantation of 1CU accommodating IOL. Twenty eyes of 10 age-matched and sex-matched patients with cataract had the same surgery but with a foldable acrylic IOL. All patients had assessments of the amplitude of accommodation, refraction, uncorrected and best corrected distance and near visual acuity, and distance corrected near visual acuity before surgery up to 12 months after surgery. Contrast visual acuities were measured 1 year after surgery. Anterior segment photography, intraocular pressure measurements, specular microscopy, and computerized topography were also performed. RESULTS: The final best corrected distance visual acuity was above 20/25 in all eyes with the 1CU and the AcrySof IOLs. The mean distance corrected near visual acuity was significantly higher in the 1CU IOL group than in the acrylic IOL group after 3 months. None of the eyes with the AcrySof IOL implants displayed an accommodative response at any examination. The peak mean amplitude of accommodation with the 1CU IOLs was observed at 3 months and was 0.5 diopters +/- 0.44 (SD). Accommodation amplitude declined after 6 months. CONCLUSION: The 1CU IOL provided additional near acuity postoperatively, but the benefit disappeared at 12 months with a concomitant decrease in accommodation amplitude owing to an increase in anterior and posterior capsular opacities.

Accommodation, Ocular↗

PubMed2005

Microkeratome-assisted phacoemulsification.

This study reports a technique in which phacoemulsification and intraocular lens (IOL) insertion are performed in conjunction with a microkeratome flap in a patient with ocular surface disease. Microkeratome-assisted phacoemulsification was performed in a 72-year-old woman with a history of trachoma during childhood. A 130 microm corneal flap was made using a microkeratome prior to phacoemulsification and IOL insertion. Lifting the flap during surgery allowed a clear view of the anterior chamber through the smooth lamellar interface created by the microkeratome blade. The flap was washed and repositioned without sutures at the end of surgery. There were no complications associated with the microkeratome flap following surgery. Visual acuity improved from hand motion to 20/200. Microkeratome-assisted phacoemulsification is a safe technique for cataract patients with diseases of the ocular surface.

Aged↗

PubMed2005

Pupil decentration and iris tilting detected by Orbscan: anatomic variations among healthy subjects and influence on outcomes of laser refractive surgeries.

PURPOSE: To investigate the anatomic variations of entrance pupil decentration and tilting angle of the iris in healthy subjects and the influence of these factors on the outcome of laser in situ keratomileusis (LASIK). SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: The degree of pupil decentration and tilting angle of the iris in 2280 eyes of 1144 myopic patients without abnormal findings by ophthalmologic examination were assessed using Orbscan. Of these, 901 eyes of 467 patients had LASIK. Multiple analysis of variance (ANOVA) was used to determine risk factors for reduction of postoperative best spectacle-corrected visual acuity (BSCVA) considering patient age, refractive power, tilting angle of the iris, pupil decentration, and corneal power. RESULTS: The mean pupil decentration in all eyes was 0.19 mm +/- 0.11 (SD) (range 0 to 0.9 mm); tilting angle of the iris was 4.06 +/- 1.41 degrees (range 0.19 to 12.69 degrees). By multiple ANOVA, refractive power, pupil decentration, and tilting angle of the iris were significant for the reduction of BSCVA. CONCLUSIONS: Some eyes with pupil decentration or tilting angle of the iris could not be detected under typical ophthalmologic examination but only with topographic examination. Attention should be paid to eyes with large pupil decentration and tilting angle of the iris because these may be risk factors for reduction of postoperative BSCVA during corneal refractive surgeries.

Adult↗

PubMed2005

The effect of periocular warming on accommodation.

PURPOSE: To investigate the effect of periocular warming on accommodation amplitude and near vision after prolonged near work in visual display terminal (VDT) workers in an office setting. DESIGN: Prospective interventional observational case series. PARTICIPANTS: Ten healthy Japanese male volunteers (mean age, 39.3+/-2 years [range, 36-43]) with a best distance corrected visual acuity (VA) of >20/20 who performed near work for 7 hours were included in the study. MAIN OUTCOME MEASURES: The differences of subjective and objective accommodations, near acuity, and pupil diameters were compared and studied in 2 experimental settings with and without periocular warming. METHODS: Two experiments were performed on each subject on 2 different days. In one experiment, the subjects wore an eye mask and closed their eyelids for 10 minutes after 7 hours of VDT work (lid closure [LC] group). In the other experiment, the subjects applied warming sheets (WSs) to their eyelids and the periocular region and wore masks for 10 minutes again after 7 hours of VDT work (WS group). Visual display terminal work was performed under the same settings on both days. Subjective and objective accommodations, near vision, and pupil diameters were measured immediately before and immediately after the resting or warming procedure and again 90 minutes after the resting or warming procedures. RESULTS: Fifty percent of eyes had an increase in the accommodation amplitude of at least 0.5 diopters immediately after application of the WSs. Forty percent of eyes still maintained the accommodation amplitude level at 90 minutes. The mean near logarithm of the minimum angle of resolution VA immediately after application of WSs and at 90 minutes significantly improved relative to the near acuity values after simple eyelid closure. CONCLUSION: Periocular warming was found to be associated with increases in subjective and objective accommodations, with a concomitant improvement in near VA. Periocular warming with disposable WSs is a simple and effective method of increasing near work-related ergonomy.

Accommodation, Ocular↗

PubMed2005

Intraocular lens implantation after atopic cataract surgery decreases incidence of postoperative retinal detachment.

PURPOSE: To investigate the efficacy of intraocular lens (IOL) implantation in reducing the incidence of postoperative retinal detachment after cataract surgery in patients with atopic dermatitis. DESIGN: Retrospective review. PARTICIPANTS: One hundred sixty-nine eyes of 126 patients who underwent cataract surgery for atopic cataract were followed for more than 1 year. None of the eyes previously had a retinal detachment or retinal detachment surgery. METHODS: The eyes were divided into 132 eyes of 95 patients with an IOL implantation (IOL group) and 37 eyes of 31 patients without an IOL implantation (aphakia group). The postoperative visual acuity and incidence of postoperative retinal detachment were compared between the 2 groups. The effects of the location of the causative retinal breaks, intraoperative posterior capsule rupture, and postoperative posterior capsulotomy on the incidence of retinal detachments were evaluated. MAIN OUTCOME MEASURES: The postoperative corrected visual acuity, incidence of postoperative retinal detachment, and influence of intraoperative posterior capsule rupture on the retinal detachment. RESULTS: The final visual acuity was better than or equal to 20/20 in 128 eyes (97.0%) of the IOL group and in 29 eyes (78.4%) of the aphakia group (P = 0.0007). Retinal detachment after an uncomplicated cataract surgery occurred in 3 eyes (2.3%) of the IOL group and in 8 eyes (25.8%) of the aphakia group (P<0.0001, Mantel-Cox). Two of 3 eyes (66.7%) in the IOL group and 1 of 8 eyes (16.7%) in the aphakia group that later developed a retinal detachment had an intraoperative posterior capsule rupture. Posterior capsulotomy by yttrium-aluminum-garnet laser did not seem to alter the incidence of postoperative retinal detachment in either the IOL (2.0%) or the aphakia group (25.0%). CONCLUSIONS: The rate of postoperative retinal detachment in eyes with IOL and no intraoperative posterior capsule rupture seems to be low. Intraocular lens implantation with capsular bag fixation may reduce the incidence of postoperative retinal detachment triggered by lens surgery for atopic cataract.

Adolescent↗

PubMed2005

Ocular surface and MUC5AC alterations in atopic patients with corneal shield ulcers.

PURPOSE: To describe MUC5AC alterations and the ocular surface disorder in atopic patients with or without corneal ulcers. METHODS: Atopic patients' eyes were divided into two groups according to the presence and absence of corneal ulceration. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface and conjunctival impression cytology and brush cytology. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and quantitative real-time PCR for MUC5AC mRNA expression. The differences related to the tear function and ocular surface examination parameters between patients with and without corneal ulceration and healthy control subjects were studied. In addition, the differences of the study parameters related to ocular surface epithelial health and inflammatory status between patient eyes with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) were investigated. RESULTS: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers, compared to patients without ulcers and controls (p < 0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared to patients without ulcers and controls (p < 0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction in goblet cell density compared to eyes without ulcers and eyes of control subjects. The mean squamous metaplasia grade was significantly higher in eyes with AKC compared to eyes with VKC (p < 0.02). The mean goblet cell density was significantly lower in eyes with AKC compared to eyes with VKC (p < 0.01). Specimens from eyes with corneal ulcers showed PAS positive mucin pickup and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared to eyes without ulcers and eyes of control subjects. MUC5AC mRNA expression was also significantly lower in eyes with AKC compared to eyes with VKC. CONCLUSIONS: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

Adolescent↗

PubMed2005

Elevated levels of human alpha -defensin in tears of patients with allergic conjunctival disease complicated by corneal lesions: detection by SELDI ProteinChip system and quantification.

PURPOSE: To analyze levels of alpha -defensin in the tears of allergic patients (with/without corneal lesions) comparing the results with those of normal control subjects. METHODS: Screening of the protein profiles of the tears of allergic patients with corneal epithelial lesions and normal controls was performed by surface enhanced laser desorption/ionization (SELDI) ProteinChip array initially. ELISA was then performed to quantify the levels of alpha -defensin in the tears of allergic patients (with/without corneal epithelial lesions) and normal control patients. RESULTS: Proteins expressing significant differences between patients and controls by SELDI analysis were examined. Several peptides with molecular weights similar to alpha -defensins were found to be expressed to a greater extent in allergic patients. ELISA was performed in tears of allergic patients and control subjects to ascertain the presence and increased expression of alpha -defensins in allergic patients. Concentrations of alpha -defensins in allergic patients with corneal epithelial lesions were significantly higher than those of allergic patients without epithelial lesions or normal controls. CONCLUSIONS: Alpha-defensins were found in greater concentrations in tears of allergic patients with corneal lesions. The antimicrobial effects of alpha -defensins may play a role in the prevention of secondary infection of corneal lesions in allergic patients. SELDI ProteinChip technology is a useful and effective tool in profiling the differential expression of proteins in tears.

Conjunctivitis, Allergic↗

PubMed2005

Hyaluronic acid-CD44 interaction mediates the adhesion of lymphocytes by amniotic membrane stroma.

PURPOSE: To demonstrate the role of intrinsic hyaluronic acid (HA) in the entrapment of inflammatory cells by amniotic membrane (AM) in vitro. METHODS: HA concentration in AM was analyzed by the sandwich protein binding assay, and the approximate molecular weight was measured by gel filtration chromatography. To localize HA in AM tissue, toluidine blue staining with and without hyaluronidase treatment was performed. Adhesion of the lymphocyte cell lines, Jurkat and Molt 4, and peripheral blood mononuclear cells (PBMC) to AM and HA-coated glass slides was analyzed in an in vitro binding assay. Flow cytometry was performed to quantify the expression of the HA receptor, CD44, in Jurkat, Molt 4, and PBMC. RESULTS: HA was present in high levels in the stroma of AM, also demonstrated by intense staining with toluidine blue. Staining was inhibited by both hyaluronidase treatment and acidic pH. Molt 4, which constitutively expressed CD44, bound to AM and HA-coated slides significantly more than Jurkat cells (CD44-). Adhesion of Molt 4 was inhibited by pretreatment with both soluble HA and anti-CD44 antibody. LPS- or TNF-alpha-treated PBMC also bound to AM and HA-coated slides and was inhibited by pretreatment with an anti-CD44 antibody. CONCLUSION: HA in AM stroma may play an important role in the entrapment of inflammatory cells including lymphocytes when used as a patch in ocular surface disease.

Cell Adhesion↗

PubMed2005

Deep lamellar keratoplasty (DLKP) in keratoconus patients using viscoadaptive viscoelastics.

PURPOSE: To demonstrate the effectiveness and safety of using viscoadaptive viscoelastics in deep lamellar keratoplasty (DLKP) for keratoconus. METHODS: A nonrandomized, comparative, interventional case series was performed on 12 eyes of 10 consecutive keratoconus patients without a history of acute hydrops. Patients were treated with DLKP using ophthalmic viscosurgical devices (OVDs) to dissociate Descemet membrane (DM) from the stroma before suturing of the donor cornea. Eight eyes were operated using Viscoat (dispersive), and 4 eyes were operated using Healon V (viscoadaptive). RESULTS: Six out of 8 eyes in the Viscoat group were successfully treated, and 2 eyes were converted to PKP because of tears in the DM. Another 3 eyes had double chambers as a result of perforations or tears in DM, which were treated by injecting air into the anterior chamber. All 4 eyes in the Healon V group were successfully operated, with 1 case with microperforation of DM during suturing. Healon V offered better control of the area to be dissociated and served as a pseudostroma that protects the exposed DM while the overlying stroma is maneuvered. CONCLUSION: Healon V is a valuable tool for performing DLKP in difficult cases such as keratoconus.

Adult↗

PubMed2005

Histopathological findings of epithelial ingrowth after laser in situ keratomileusis.

PURPOSE: To investigate the histopathological features of epithelial ingrowth after laser in situ keratomileusis (LASIK). METHODS: Five epithelial ingrowth specimens of 4 patients (2 to 17 months after initial LASIK) were examined. The lesions were surgically removed and examined using light and transmission electron microscopy. RESULTS: Early epithelial ingrowth was clinically observed as faint opacities with demarcation lines and epithelial pearls. Late epithelial ingrowth was observed as homogeneous whitish masses. Histopathologically, early epithelial ingrowth consisted of multilayered squamous epithelium resembling normal corneal epithelium, whereas late ingrowth was made up of clumps containing amorphous materials with scarce cellular elements. CONCLUSIONS: Our findings suggest that clinical appearance and histopathology of epithelial ingrowth from LASIK flap margins differ in early and late stages, which might reflect proliferative activity of the lesions.

Adult↗

PubMed2005

The effect of antireflection film use on blink rate and asthenopic symptoms during visual display terminal work.

PURPOSE: To investigate the effect of visual display terminal antireflection (AR) films on blink rate and subjective symptoms of asthenopia. METHODS: This was a nonrandomized, prospective clinical trial in which 7 healthy volunteers underwent blink rate measurements with a blink rate recording system while viewing a DVD on a computer display for 10 minutes. The measurements were carried out without an AR film on terminal displays initially. The same tasks were performed on the next day with an AR film on the displays. The subjects were also required to score their symptoms of asthenopia on a visual analog scale before and just after DVD viewing. The changes in blink rate and asthenopia scores with AR film use were assessed by the Student t test. RESULTS: The mean baseline blink rate was 15.7 +/- 5.9 blinks /min, which decreased significantly to 9.6 +/- 4.3 blinks/min after DVD viewing without an AR film (P < 0.05). The mean baseline and final blink rates for DVD viewing with an AR film were 14.6 +/- 9.2 and 14.3 +/- 9.2 blinks/min, respectively. There were no significant differences between baseline and final blink rates after DVD viewing with an AR film (P > 0.05). The mean cumulative visual analog asthenopic symptom score after DVD viewing without an AR film was 72 +/- 18% compared with the mean cumulative symptom score of 52 +/- 11% after DVD viewing with an AR film. The difference was statistically significant (P < 0.05). CONCLUSIONS: Visual display terminal work appears to be associated with asthenopic symptoms and decreased blink rates. The use of AR films on computer displays may prevent both reflections of light from screen surfaces and reduction in blink rates resulting in fewer asthenopic symptoms.

Adult↗

PubMed2005

Ocular surface findings in Hallopeau-Siemens subtype of dystrophic epidermolysis bullosa: report of a case and literature review.

PURPOSE: This article describes the clinical features and long-term changes in corneal sensitivity, tear function, and impression cytology findings in a patient with recessive dystrophic epidermolysis bullosa (DEB). METHODS: The patient underwent best-corrected Landolt visual acuity measurements, slit-lamp examinations, anterior segment photography, Schirmer test with anesthesia, tear film break-up time, corneal fluorescein and Rose-Bengal staining, assessment of corneal sensitivity, and conjunctival impression cytology at the initial and final visits. RESULTS: The patient had a recurrent corneal erosion in the right eye and a painful corneal blister with extensive superficial punctuate keratopathy in the left eye, which remained refractory to treatment with patching, lubricants, and antibiotic ointments for 10 weeks. The corneal disease in both eyes responded swiftly to topical fibronectin, topical nonpreserved tears, vitamin A ointment, and therapeutic soft contact lenses. Maintenance treatment was continued with preservative-free topical tear drops and vitamin A ointment. Corneal disease did not recur in the patient during the follow-up of 29 months. The mean corneal sensitivity and tear film break-up time were decreased initially in both eyes and attained normal values with treatment. Impression cytology revealed squamous metaplasia, loss of cellular cohesion, and total absence of goblet cells before treatment, all of which were observed to be normalized at the final follow-up. CONCLUSIONS: The ocular surface disease in DEB was characterized by low corneal sensitivity, disorder of tear quality, decreased cellular cohesion, squamous metaplasia of the conjunctiva, and goblet cell loss. Close follow-up for ocular complications in DEB is essential and a pathophysiology-oriented approach to the epithelial disease may not only provide rapid healing but might prevent recurrences as well.

Administration, Topical↗

PubMed2005

Successful topical application of a new antifungal agent, micafungin, in the treatment of refractory fungal corneal ulcers: report of three cases and literature review.

PURPOSE: To report the efficacy of topical application of a new antifungal agent, micafungin (MCFG), in the treatment of yeast-related corneal ulcers. DESIGN: Noncomparative interventional case reports. PARTICIPANTS: Three patients with yeast-related corneal ulcer after keratoplasty recalcitrant to conventional antifungal treatment for 4 weeks were recruited in this study. METHODS: Topical 0.1% antifungal MCFG eye drops were applied in 3 patients with yeast-related corneal ulcer every hour while awake until epithelialization. After epithelialization, the frequency of eye drops was reduced to 5 times a day. MCFG eye drops were discontinued 1 month after the disappearance of stromal infiltration in each case. The patients underwent best corrected visual acuity (BCVA) measurements, slit-lamp examination, fluorescein-dye staining, and anterior segment photography. Corneal scrapings and cultures of surgical materials were also performed. MAIN OUTCOME MEASURES: Changes in ulcer size, stromal infiltration, fluorescein dye staining, and BCVA were looked for. RESULTS: All corneal ulcers epithelialized within 14 days after commencement of application of 0.1% MCFG eye drops. Yeasts were detected from corneal smears in all eyes. Two cases revealed positive culture isolates for Candida albicans and Candida parapsilosis. No recurrence of fungal keratitis was observed in any of the cases throughout the follow-up periods. CONCLUSION: Topical 0.1% MCFG eye drops seem to be an effective and a promising option in the treatment of refractory yeast-related corneal ulcers.

Administration, Topical↗

PubMed2005

Prostaglandin D2 induces chemotaxis in eosinophils via its receptor CRTH2 and eosinophils may cause severe ocular inflammation in patients with allergic conjunctivitis.

PURPOSE: Eosinophils are known to have important roles in the pathogenesis of allergic conjunctivitis. Prostaglandin (PG) D2, which has been implicated as a factor in allergic diseases, is known to have chemotactic activity for eosinophils. Its receptor, chemoattractant receptor homologous molecule expressed on TH2 (CRTH2), serves as a receptor for PGD2 and has been reported to mediate PGD2-dependent migration of eosinophils. In the present study, both eosinophil toxic activity for corneal epithelial cells and chemotaxis induced by PGD2 in normal volunteers were investigated. Expression of CRTH2 in normal subjects was also measured. METHODS: Primary cultured corneal epithelial cells and eosinophils in serum from normal volunteers were used and a human corneal epithelial cell line was established. Studies were performed with/without amniotic membrane. CRTH2 expression on eosinophils was assessed by flow cytometry. Chemotaxis experiments were performed using a modified Boyden chamber technique. RESULTS: Corneal epithelial cells cultured with eosinophils showed higher floating epithelial cells and epithelial defect than those cultured in the absence of eosinophils. Flow cytometry analysis revealed that eosinophils expressed CRTH2. PGD2 induced chemotaxis of eosinophils. CONCLUSIONS: Corneal epithelial damage might be caused by eosinophils, which are recruited by PGD2 secretion via CRTH2 expressed on eosinophils.

Cell Line↗

PubMed2005

Atopic ocular surface disease: implications on tear function and ocular surface mucins.

PURPOSE: To describe tear function, mucin alterations, and ocular surface disorder in patients with atopic diseases. METHODS: Subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) assay, and fluorescein and rose Bengal staining of the ocular surface. Conjunctival impression cytology and brush cytology were also conducted. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and RT-PCR for MUC5AC mRNA expression. Differences related to tear function and ocular surface examination parameters among patients with and without corneal ulceration and healthy control subjects were studied. RESULTS: Mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers compared with patients without ulcers and controls (P<0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared with patients without ulcers and controls (P<0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction of goblet cell density compared with eyes without ulcers and control subjects. Specimens from eyes with corneal ulcers showed PAS (+) mucin pick up and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared with in eyes without ulcers and control subjects. CONCLUSIONS: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression are important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

Corneal Ulcer↗

PubMed2005

Tear film and ocular surface abnormalities after eyelid tattooing.

A 45-year-old woman who underwent eyelid tattooing 20 years earlier presented with decreased left vision and eye discomfort. Her ocular history revealed an uneventful LASIK procedure 4 years previously with epithelial problems of the flap followed by S. aureus keratitis. Resultant corneal opacity necessitated a deep lamellar keratoplasty performed 9 months prior to admission followed by frequent epithelial problems. At the time of admission, her left eye had a corneal epithelial defect and both lower eyelid margins revealed subepidermal pigmentation and keratinization. Her initial examination revealed tear instability with increased ocular surface staining scores and advanced tear film lipid layer abnormality in both eyes. Meibography showed bilateral total meibomian gland dropout. Treatment with autologous serum eye drops resulted in full epithelialization. Meibomian gland disease-specific therapy did not result in any change in breakup time, vital staining scores, tear film lipid layer interferometry grades, or glandular dropout state.

Eyelid Diseases↗

PubMed2005

Selective suppression of pathologic, but not physiologic, retinal neovascularization by blocking the angiotensin II type 1 receptor.

PURPOSE: To investigate the anti-inflammatory and anti-angiogenic effects of telmisartan, an angiotensin II type 1 receptor (AT1-R) antagonist, on ischemia-induced retinal neovascularization. METHODS: C57BL/6 neonatal mice were reared in an 80% concentration of oxygen from postnatal day (P)7 to P12, followed by room-air breathing until P17, to induce ischemia-initiated retinal neovascularization (i.e., a murine model of ischemic retinopathy). Tissue localization of AT1-R was examined by immunohistochemistry for murine retinal wholemounts and human fibrovascular tissues excised at vitrectomy for proliferative diabetic retinopathy. Animals received intraperitoneal injection of telmisartan or vehicle. A concanavalin A lectin perfusion-labeling technique was used to evaluate the areas of physiological and pathologic retinal new vessels and the number of leukocytes adhering to the vasculature. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA. RESULTS: Vessels in human fibrovascular tissues and the murine retinas were positive for AT1-R. Pathologic (P < 0.01), but not physiologic (P > 0.05), retinal neovascularization was significantly suppressed in telmisartan-treated mice compared with vehicle-treated animals. The number of adherent leukocytes (P < 0.01) was also significantly reduced, together with retinal ICAM-1 levels (P < 0.01) in the telmisartan-treated group compared with the control group. No significant difference was detected in retinal VEGFR-2 levels between the two groups, whereas retinal VEGFR-1 levels in the telmisartan-treated group were significantly (P < 0.05) lower than in the vehicle-treated group. CONCLUSIONS: The present findings suggest that the AT1-R signaling blockade leads to the selective suppression of pathologic, but not physiological, retinal neovascularization through the inhibition of the inflammatory processes related to pathologic neovascularization.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

D-beta-hydroxybutyrate protects against corneal epithelial disorders in a rat dry eye model with jogging board.

PURPOSE: The purpose of this study was to establish a rat dry eye model of corneal epithelial disorders by inducing improper tear dynamics and change in blink frequency. The protective effect of d-beta-hydroxybutyrate (HBA) on the corneal epithelia was also investigated. METHODS: A series of treatments were performed under continuous exposure to low-humidity airflow. Rats were placed on a jogging board (JB) made of a plastic pipe for 7.5 h/d, and, for 16.5 hours, they were placed in individual cages without JB treatment. The resultant changes in tear dynamics and corneal epithelial structure were then analyzed. Five days after the rats were exposed to the treatment, eyes that showed corneal fluorescein staining were examined, to investigate the effect of HBA, by administration of eye drops containing 80 mM HBA four times daily during JB treatment for 5 days. RESULTS: Significant reductions in blink frequency, Schirmer score, and tear clearance were recorded during JB treatment in eyes that showed persistent punctate staining of almost one half of the corneal surface. The application of HBA-containing eye drops significantly reduced the punctate staining compared with the initial or phosphate-buffered saline-treated eyes. CONCLUSIONS: This rat dry eye model, established by repeated JB treatment in desiccating conditions, induced abnormal tear dynamics and superficial punctate keratopathy similar to that in humans. These findings suggest the potential clinical application of HBA in corneal surface epithelial disorders in patients with moderate to mild dry eye.

3-Hydroxybutyric Acid↗