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Biomedical subjects

Kazuo Tsubota

Publications and source records attributed to Kazuo Tsubota.

At least 37 records · Page 2Linked to original sources

Smoking associated with damage to the lipid layer of the ocular surface.

PURPOSE: To evaluate the effects of smoking on ocular surface. DESIGN: Prospective, comparative, interventional case series. METHODS: setting: Institutional. study population: Sixty smokers (33 men, 27 women) and 34 healthy subjects (18 men, 16 women) were enrolled into this study. Patients with associated ophthalmic or systemic diseases, and history of contact lens use and ocular surgery were excluded. The duration of average smoking was 13.1 years (range 5 to 35 years). INTERVENTION: Ocular surface was evaluated by measuring corneal and conjunctival sensitivity, surface staining with fluorescein, tear film breakup time, Schirmer 1 test, and conjunctival impression cytology. Dry eye symptoms were scored by questionnaire. Kinetic analysis of sequential tear interference images obtained by a DR-1 tear lipid layer interferometry was used to investigate the precorneal lipid layer spread. Results were compared with a control group. MAIN OUTCOME MEASURES: Comparison of subjective complaints with objective parameters in cigarette smokers and normal subjects. RESULTS: In the smoker group, the mean Schirmer 1 test value was 10.8 mm (range 8 to 14 mm). The mean breakup time was 5.3 seconds (range 1 to 10 seconds), the average conjunctival sensitivity was 26.2 mm (range 0 to 45 mm), and the average central corneal sensitivity was 37.6 mm (range 5 to 60 mm). There was no statistically significant difference in goblet cell densities or in Schirmer 1 test values between smokers and controls (P > .05). Higher grades of lipid layer changes were observed in smokers by DR-1 interferometry kinetic analysis. CONCLUSIONS: Smoking has deteriorating effects on the lipid layer of precorneal tear film.

Adult↗

Successful tear lipid layer treatment for refractory dry eye in office workers by low-dose lipid application on the full-length eyelid margin.

PURPOSE: To test tear lipid layer treatment by low-dose lipid application on the full-length eyelid margin for the treatment of office workers with dry eyes refractory to conventional treatments. DESIGN: Prospective interventional case series. METHODS: Thirty eyes of 30 office workers with dry eyes with dark tear interference images, which did not respond to conventional treatments, were included. To supply lipid using a commercially available nonpreserved topical medication having both polar and nonpolar lipid base, ofloxacin eye ointment (Santen Pharmaceutical, Osaka, Japan) was selected. Low-dose ofloxacin ointment application on the full-length eyelid margin was carried out three times a day for two weeks. The symptom of ocular dryness using a visual analog scale, tear interferometry to assess lipid layer thickness (LLT), corneal fluorescein staining, tear-film breakup time (BUT), and meibum expressibility gradings were compared. RESULTS: After the treatment, the symptom score of ocular dryness decreased from 91.4 +/- 11.9 to 33.6 +/- 21.0 (P < .0001), LLT increased from 39 +/- 4 nm to 161 +/- 91 nm (P < .0001), BUT was prolonged from 2.6 +/- 1.6 seconds to 4.8 +/- 2.1 seconds (P = .01), and meibum expressibility gradings decreased from 2.8 +/- 1.3 to 1.6 +/- 1.3 (P = .0005). CONCLUSION: For office workers with refractory dry eyes, tear lipid layer treatment by low-dose ointment applied on the full-length eyelid margin was shown to be an effective approach. The applied lipid formed a uniform lipid layer, which contributed to tear stability, leading to the improvement of the symptom.

Adult↗

Comparison of deep lamellar keratoplasty and penetrating keratoplasty for lattice and macular corneal dystrophies.

PURPOSE: To compare the therapeutic outcomes after deep lamellar keratoplasty (DLKP) and penetrating keratoplasty (PKP) in patients with lattice corneal dystrophy (LCD) and macular corneal dystrophy (MCD). DESIGN: Age-matched control study. METHODS: We reviewed the clinical records of 84 eyes with LCD or MCD who had DLKP (41 eyes) or PKP (43 eyes). Primary pathology consisted of 60 eyes with LCD and 24 eyes with MCD. DLKP was performed by either removing stromal tissue gradually, or by viscodissection of Descemet's membrane. Graft clarity, best-corrected visual acuity (BCVA), endothelial density, and complications were compared between DLKP and PKP, as well as between LCD and MCD. RESULTS: All 84 eyes showed a postoperative improvement in visual acuity. The median final BCVA was not significantly different between PKP and DLKP groups. Endothelial cell loss rates were similar for DLKP and PKP. While the MCD-DLKP group showed progressive decrease in endothelial density, this was not observed in the LCD-DLKP group after surgery. In the DLKP group, most of the complications occurred intraoperatively or in the early phase, whereas late phase complications such as endothelial rejection and secondary glaucoma were the main complications in the PKP group. CONCLUSIONS: PKP is no longer an automatic choice for the surgical treatment for LCD and MCD; DLKP seems to be a safe alternative. While DLKP is a favorable method for LCD, MCD may not be a good candidate, as it might show progressive decrease in the corneal endothelium postoperatively.

Adult↗

Optical aberrations and visual disturbances associated with dry eye.

Optical aberrations and visual disturbances are associated with dry eye, although visual impairment is often not detected by conventional visual acuity testing. The newly developed functional visual acuity (FVA) device allows continuous dynamic evaluation of distance visual acuity and assessment of the effect of natural tear film status on dynamic visual function. Similarly, to detect corneal surface irregularities during sustained eye opening in dry eye subjects, a new tear stability analysis system (TSAS) has been developed. Both FVA and TSAS measurement systems seem to be effective tools in the assessment of dynamic visual acuity changes in dry eye and normal subjects. Both methods were also found to be helpful in the evaluation of the outcome of management of dry eye disease. FVA testing has been suggested to be an important indication of an individual's performance in relation to certain daily activities, such as driving, reading and working at a video display terminal. This review provides illustrations of results obtained from FVA and TSAS systems.

Astigmatism↗

Changes observed in keratolimbal allograft.

OBJECTIVE: To study the incidence and clinical characteristics of presumed immunologic reactions in limbal grafts after keratolimbal allograft(KLAL). METHODS: A total of 121 KLALs performed in consecutive 85 eyes of 78 patients with total limbal stem-cell deficiency were analyzed retrospectively. Mean follow-up period was 46.6 months. Three types of limbal graft changes classified as epithelial defects, acute edema, and vascular engorgement were analyzed as probable signs of immunologic rejection. RESULTS: One or more changes in limbal grafts were observed after 16 KLALs (13.1%). All but 1 eye used systemic and local immunosuppression using corticosteroid and cyclosporine A, and most of the changes developed within 3 months postoperatively. All but 2 eyes developed epithelial breakdown in the central cornea, and 12 corneas underwent conjunctivalization. The rate of corneal epithelialization in eyes with limbal graft changes was significantly worse than those without the changes (P < 0.0001). Histologic examination in eyes with the limbal graft changes revealed high incidence of lymphocyte infiltration. CONCLUSIONS: Presumed limbal graft rejection occurred in approximately 13% of cases after KLAL. Suppression of the immune reaction remains a key to success in KLAL.

Adolescent↗

Tear film lipid layer alterations in allergic conjunctivitis.

PURPOSE: To assess the alterations of the tear film lipid layer and tear functions in patients with seasonal allergic conjunctivitis (SAC) and to compare the results with healthy control subjects. METHODS: Seventy-eight eyes of 39 consecutive patients diagnosed as SAC (mean age 32.6 years; 11 male, 28 female) as well as 20 eyes of 10 healthy control subjects (mean age 32.5 years; 6 male, 4 female) underwent slit-lamp examinations, tear film breakup time measurements (BUT), corneal fluorescein stain scoring, Schirmer test, and tear film lipid layer interferometry. The 2 groups were then compared for the examined parameters. RAST and serum IgE level evaluations were also carried out in the patients to confirm the diagnosis of allergy. RESULTS: The mean BUT was 3.4 +/- 1.5 seconds in patients with SAC compared with the mean value of 12.4 +/- 2.4 seconds in the controls (P < 0.05). There were no significant differences in relation to Schirmer test values between the 2 groups; 78% of the patients with SAC had grade 3 or above dry eye change in tear film lipid layer interferometry, whereas none of the controls had an interferometry grade greater than 3 (grade 1-2 normal; grade 3-4 dry eye; grade 5 severe dry eye). Eyes with SAC had significantly higher tear film lipid layer thickness ranges compared with the control eyes (P < 0.05). CONCLUSION: SAC was associated with advanced tear instability and thickening of the tear film lipid layer. Evaluation of the tear film lipid layer thickness might be useful in the assessment of the extent of dry eye disease and the treatment outcomes in patients with allergy.

Adult↗

Ocular surface reconstruction for thermal burns caused by fireworks.

PURPOSE: To describe 6 eyes with severe firework-related ocular surface injuries that were treated by limbal stem cell transplantation combined with amniotic membrane transplantation (AMT). METHODS: Six eyes of 6 patients with firework-related ocular injuries were retrospectively studied. All subjects were men, with age ranging from 9 to 26 years. All patients were in chronic stage of thermal injury, and all had total limbal stem cell dysfunction and subsequent conjunctival fibrosis. They had limbal stem cell transplantation (1 had an allograft and 5 had autograft transplantation) combined with AMT to restore vision. Mitomycin C was used in 1 eye intraoperatively. RESULTS: After ocular surface reconstruction using limbal stem cell transplantation combined with AMT, corneal epithelialization was achieved in 4 eyes after a mean duration of 20.8 +/- 12.2 days (range, 4-33 days). After a mean follow-up period of 36 months (range, 5-87 months), marked reduction of fibrosis was noted in all eyes. At last examination, the corneal surface was covered by corneal-phenotype epithelium in 4 eyes, and the remaining 2 eyes had conjunctivalization. The cornea was optically clear in 3 eyes, with corrected visual acuity of 20/100 in these 3 eyes. Both eyes that developed conjunctivalization had massive fibrosis preoperatively and severe eyelid deformities. CONCLUSION: Although severe firework-related ocular surface injuries were difficult to treat, limbal stem cell transplantation combined with AMT enable some success in cosmetic and visual outcome. Management of eyelid abnormalities and ocular surface fibrosis seemed to be a key to success in visual rehabilitation.

Adolescent↗

Quantitative evaluation of the early changes in ocular surface inflammation following MMC-aided papillary resection in severe allergic patients with corneal complications.

BACKGROUND: Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) are chronic inflammatory allergic diseases that are associated with some common conjunctival and corneal complications.1 The clinical corneal manifestations of both entities may include superficial punctate keratitis, macroerosions, corneal ulceration, plaque formation, corneal neovascularization, and lipid infiltration. PURPOSE: To quantitatively evaluate the early ocular surface inflammation before and after mitomycin C (MMC)-aided papillary resection in severe allergy patients with corneal complications. METHODS: Three eyes with VKC and 5 eyes with AKC were included in this study. All eyes had cobblestone-like papillae on the upper tarsal conjunctiva and corneal complications such as corneal ulcers, defect, or erosions that were refractory to conventional treatment of more than 2 weeks. Papillary resection with intraoperative 0.05% MMC application for 5 minutes on the palpebral conjunctiva was carried out in all eyes. Corneal and conjunctival findings were evaluated before and 1 week and 2 weeks after surgery. Brush cytology (BC) and evaluation of tear eosinophilic cationic protein (ECP) levels by radioimmunoassay techniques were performed as well pre- and postoperatively. RESULTS: Corneal and conjunctival complications resolved in all patients within 7 days after resection. Postoperative tear ECP levels decreased significantly with papillary resection (P< 0.05). Concomitant brush cytology showed a significant decrease in the number of eosinophils and neutrophils following papillary resection (P < 0.05). CONCLUSION: MMC-aided papillary resection provided a dramatic decrease in ocular surface inflammation as evidenced by decrease in the number of inflammatory cells as well as tear ECP levels with a rapid improvement of clinical corneal and conjunctival findings.

Adolescent↗

Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.

PURPOSE: To evaluate the safety and efficacy of an original warm moist air device on tear functions and ocular surface of patients with simple meibomian gland dysfunction (MGD). METHODS: Fifteen patients with simple MGD and 20 healthy volunteers were recruited in an initial prospective interventional clinical trial to evaluate the safety and short-term effects of the warm moist air device. The device was applied to the eyes of the subjects for 10 minutes. Temperatures of the eye lids and corneas were measured with an infrared thermometer. Symptoms of ocular fatigue were scored using visual analog scales (VASs). Schirmer test, tear film break-up time (BUT), DR-1 tear film lipid layer interferometry, fluorescein staining, and rose bengal staining were also performed before and after the application of the eye steamer. After the initial study, another 2-week prospective clinical trial was carried out in 10 patients with MGD who received the warm moist air treatment. Ten other patients were also recruited and received warm compress treatment with hot towels for 2 weeks to evaluate the long-term effects of the warm moist air device and the warm compresses on tear film lipid layer thickness and ocular surface health. The warm moist air device and the warm compresses were applied for 10 minutes twice a day. The changes in VAS scores for symptoms, BUT values, fluorescein, and rose bengal staining scores were examined before and after each treatment during the second trial. RESULTS: VAS scores of ocular fatigue improved significantly with short- and long-term applications of the warm moist air device in both studies. The mean corneal surface and eye lid temperatures showed significant elevation within safe limits 10 minutes after the moist air application. The mean BUT prolonged significantly in the patients receiving warm moist air applications but did not change significantly in those treated with warm compresses. DR-1 tear film lipid layer interference showed evidence of lipid expression in the patients and controls, with thickening of the tear film lipid layer after 10 minutes of warm moist air device use. In the 2-week trial, tear film lipid layer thickness increased in both warm moist air device and warm compress groups, with a greater extent of increase in the warm moist air device group. CONCLUSION: Warm moist air device use provided symptomatic relief of ocular fatigue and improvement of tear stability in patients with MGD. The new warm moist air device seems to be a safe and promising alternative in the treatment of MGD.

Aged↗

Ocular surface epithelial cells up-regulate HLA-G when expanded in vitro on amniotic membrane substrates.

PURPOSE: To study the modulation of immunoregulatory genes in ocular surface epithelial cells cultured on amniotic membrane (AM). METHODS: Microarray analysis was performed in a conjunctival epithelial cell line (CCL20.2) expanded on denuded AM. Among the genes that were upregulated by an AM substrate compared with collagen-coated dishes, the fetal nonclassic major histocompatibility complex molecule, HLA-G, was found to be the only immunoregulatory gene up-regulated by more than 2.5-fold. Because CCL20.2 is contaminated by HeLa cells, expression of HLA-G mRNA was confirmed in primary-cultured limbal (LE) and conjunctival epithelial (CE) cells by reverse transcriptase-polymerase chain reaction (RT-PCR), semiquantitative real-time PCR, immunocytochemistry, and Western blot analysis. A functional assay was performed using an HLA-G-transfected K-562 human erythroleukemia cell line. RESULTS: Freshly dissociated limbal epithelial cells express HLA-G mRNA; however, protein levels were low. Western blots and immunocytochemistry showed that both LE and CE cells upregulated the HLA-G protein when cultured on collagen-coated dishes and on AM. HLA-G mRNA levels were significantly higher in CE cultured on AM compared with collagen. Natural killer (NK) cell-induced cell lysis of an HLA class 1-negative K-562 human erythroleukemia cell line was slightly reduced when transfected with LE-derived HLA-G mRNA. CONCLUSION: CE and LE cells express functional HLA-G when expanded ex vivo, which may affect inflammation and immune reaction when transplanted to the ocular surface.

Amnion↗

Association between meibomian gland changes and aging, sex, or tear function.

PURPOSE: To study changes in the lid margin and meibomian glands and their association with aging, sex, and tear function. METHODS: We examined 354 eyes in 177 subjects (76 men and 101 women; 21-93 years; mean age, 63.0 +/- 14.3 years) with no ocular symptoms or ocular surface disorders. Anatomic changes in the lid margin were studied using slit-lamp biomicroscopy. Meibomian gland function and morphology were evaluated on the basis of meibum expression and meibography, respectively. Tear function and ocular surface epithelium were assessed with the Schirmer test, by tear film break-up time, and with a fluorescein staining test. RESULTS: Eyes with abnormal lid margin anatomy, hyposecretion of meibum, and meibomian gland dropout were seen in 26 (7.3%), 46 (12.4%), and 68 eyes (18.6%), respectively, with a significant association between each finding and aging (P = <0.0001, 0.0498, and <0.0001, respectively). In patients < or =69 years of age, no significant association was found between meibomian gland-related findings and sex. However, a high incidence of abnormal lid margin and gland dropout was noted in men > or =70 years of age compared with women. No significant association was found between changes in the lid margin and meibomian glands and tear function in patients > or =40 years of age. CONCLUSION: Among symptom-free subjects, we found that changes in the lid margin and meibomian glands were closely related to aging. Among elderly subjects, changes in the anatomic lid margin and meibomian gland morphology were observed more frequently in men than in women. Tear function showed no association with either changes in the lid margin or function of the meibomian glands.

Adult↗

Mechanisms of giant papillary formation in vernal keratoconjunctivitis.

PURPOSE: Tissue remodeling, known to accompany exacerbation of bronchial asthma (BA) and characterized by thickening of reticular basement membrane, increased fibrosis, and angiogenesis, is believed to be an important mechanism in giant papillary formation in vernal keratoconjunctivitis (VKC). This study was conducted to confirm the difference of tissue remodeling between BA and VKC and to determine the most relevant factor for VKC exacerbation. METHODS: Histopathologic analysis of conjunctival specimens from 6 patients with VKC and 4 normal controls was performed. Immunohistochemistry tests for collagen types 1, 3, and 5, fibronectin, laminin (a marker of the basement membrane of the epithelium or vessels), fibroblast (prolyl 4-hydroxylase), and alpha-smooth muscle actin (alpha-SMA) were performed. Morphometric analysis evaluated immunoreactive areas for collagens and fibronectin and the number of cell nuclei in VKC papillae and normal control specimens. RESULTS: In histopathologic sections of VKC papillae, mononuclear cells were mainly observed in the central region and granulocytes preferentially in the peripheral stroma. Immunohistochemistry showed increased vascularity and existence of fibroblasts and alpha-SMA-positive cells in VKC papillae. Morphometric analysis showed that the number of cell nuclei in VKC papillae was 7.3 times higher versus in normal controls (P < 0.05). Furthermore, the immunoreactive area for fibronectin was 4.5 times larger versus in normal controls (P < 0.05), although collagens were not significantly different between the 2 groups. CONCLUSION: Giant papillary formation in VKC is thought to occur in relation to tissue remodeling. However, the most relevant factor for the exacerbation of VKC seems to be inflammation rather than fibrosis.

Actins↗

Deep anterior lamellar keratoplasty.

PURPOSE OF REVIEW: Recent advances in surgical technique have promoted a paradigm shift in the surgical treatment of corneal disease. Penetrating keratoplasty is now being replaced by various types of lamellar techniques that aim to replace damaged tissue only, while maintaining healthy tissue intact. This review focuses on recent advances in deep anterior lamellar keratoplasty. RECENT FINDINGS: The concept of creating a deep lamellar bed for lamellar keratoplasty is not new, but exposing Descemet's membrane was a tedious, time consuming procedure. New techniques that use air and ophthalmic viscosurgical devices to directly expose Descemet's membrane have dramatically reduced surgery time, while improving the safety of performing surgery. The indications for deep anterior lamellar keratoplasty have expanded from keratoconus and hereditary dystrophies, to include severe ocular surface disease and cases following infection and corneal perforation. SUMMARY: Deep anterior lamellar keratoplasty can be considered as the first choice of surgery for a wide range of corneal disease, with bullous keratopathy as the only absolute contraindication.

Corneal Diseases↗

The features of dry eye disease in a Japanese elderly population.

PURPOSE: The purpose of this study is to assess the features of dry eye disease in a Japanese elderly population. METHODS: One hundred thirteen left eyes of 113 pensioners (50 males, 63 females; mean age, 67.5 +/- 5.7 years) aged over 60 years were recruited in this study. The subjects underwent careful slit-lamp examinations of the conjunctiva, ocular surface, and the eye lids. Tear film breakup time (BUT) examinations, Schirmer test-I, and fluorescein staining of the ocular surface and transillumination of the eyelids were also performed. Dry eye symptomatology was assessed with a symptom questionnaire. Japanese Dry Eye Diagnostic Criteria were used in this study. RESULTS: Ocular tiredness, irritation, dryness, and foreign body sensation were the most frequently reported symptoms by the patients. A total of 73.5% of the eyes had definite dry eyes. A total of 39.8% of the eyes had a Schirmer test reading <5 mm. Mean Schirmer test value was 9.4 +/- 7.8 mm. The mean BUT score was 4.0 +/- 2.8 seconds. A total of 76.9% of the eyes had positive fluorescein staining of the cornea. Meibomian gland dysfunction and conjunctivochalasis were found as frequent factors in relation to dry eye disease with meibomian grand dropout showing positive correlation with tear instability. CONCLUSION: Qualitative and quantitative disorders of the tear film were far more common than recognized in this population of elderly subjects, meibomian gland dysfunction being the most common associate of the tear film disorder and dry eye status. Conjunctivochalasis (conjunctival laxity), although commonly associated with dry eye disease in the elderly, was observed not to be related to age or gender in this study.

Age Factors↗

Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation: therapeutic challenges.

We present the first child case of pseudomembranous conjunctivitis accompanied by an extensive corneal ulcer with acute graft-versus-host disease (GVHD) after cord blood stem cell transplantation (CBSCT). The histopathology of the pseudomembrane and the ocular changes following its excision were investigated specifically. One week after the excision of pseudomembrane, the extensive corneal epithelial defects had totally disappeared. Pseudomembrane excision may be an effective method of treatment in corneal epithelial defects observed after GVHD.

Acute Disease↗

Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing.

PURPOSE: The involvement of downstream messengers of transforming growth factor (TGF)-beta in the differentiation of corneal fibroblasts into myofibroblasts was investigated. The effects of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 upregulated by TGF-beta were examined in human corneal fibroblasts, and the possible involvement of IGF axis components in corneal wound healing was assessed in a mouse model. METHODS: Human corneal fibroblasts were incubated with TGF-beta2 or IGF-I, to investigate IGF-I, IGF-II, IGFBP-3, type I collagen, and alpha-smooth muscle actin (alpha-SMA) mRNA, as well as IGFBP-3 protein expression, during myofibroblast differentiation. DNA synthesis was evaluated with a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. IGFBP-3 mRNA expression, protein expression, and immunolocalization were investigated in mouse corneas after photorefractive keratectomy (PRK). RESULTS: TGF-beta2 treatment induced expression of IGF-I and IGFBP-3 mRNA and of IGFBP-3 protein in human corneal fibroblasts. TGF-beta2 and IGF-I both stimulated expression of type I collagen. TGF-beta2 but not IGF-I potently stimulated alpha-SMA mRNA expression. IGF-I potently stimulated basal DNA synthesis, whereas IGFBP-3 inhibited it. IGF-I potently stimulated proliferation of TGF-beta2-activated myofibroblasts without reversing the activated fibrogenic phenotype, whereas IGFBP-3 suppressed IGF-I-induced proliferation of corneal fibroblasts. IGFBP-3 mRNA and protein increased in mouse corneas soon after PRK, when in vivo immunostaining of the corneas showed expression of IGFBP-3 in the deep layer of the corneal stroma. CONCLUSIONS: These results suggest that during corneal wound healing, TGF-beta stimulates IGF axis components, whereas IGFBP-3 may modulate IGF-I-induced myofibroblast proliferation to suppress corneal mesenchymal overgrowth.

Actins↗

Strip meniscometry: a new and simple method of tear meniscus evaluation.

PURPOSE: To investigate the applicability and efficacy of a new and simple method of quantification of the volume of tear meniscus, termed "strip meniscometry," in the diagnosis of the dry eye syndromes in a prospective controlled study. METHODS: One hundred eyes of 50 patients with dry eye (19 males; 31 females) aged between 18 and 76 years (mean, 54.3 years), as well as 80 eyes of 40 normal subjects aged from 15 to 70 years (mean, 50.8 years; 12 males, 28 females) were recruited in this study. The patients and the control subjects underwent strip meniscometry for 5 seconds, tear film lipid layer interferometry, tear film break-up time measurement, and ocular surface vital staining with fluorescein and rose bengal dyes and the Schirmer-1 test. RESULTS: Strip meniscometry scores correlated with tear quantity and stability, ocular surface staining scores, and lipid layer interferometry grades and improved after 2 weeks of punctal plug occlusion. CONCLUSIONS: Strip meniscometry is a swift, noninvasive, promising new method that is expected to find application in the diagnosis and evaluation of the outcome of treatment of dry eye syndromes.

Adolescent↗

Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.

PURPOSE: A recent study revealed that angiotensin receptor signaling mediates ocular inflammation and neovascularization. It was also found that prorenin undergoes nonproteolytic activation leading to upregulation of the renin-angiotensin system (RAS) when prorenin receptor interacts specifically with the handle region of prorenin. The purpose of the present study was to elucidate the role of the receptor-dependent nonproteolytic activation of prorenin in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in Long-Evans rats by a single intraperitoneal injection of 100 microg lipopolysaccharide (LPS). Tissue localization of total prorenin, prorenin receptor, and activated prorenin in the EIU retina was examined by immunohistochemistry. To inhibit the prorenin receptor-mediated upregulation of the RAS, a decoy handle-region peptide (HRP) was intraperitoneally administered 24 hours before and immediately after the injection of LPS. Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. In addition, leukocyte infiltration into the vitreous cavity and protein concentration in the anterior chamber were also measured. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, and C-C chemokine ligand (CCL) 2/monocyte chemotactic protein (MCP)-1 were examined by RT-PCR and ELISA. RESULTS: Retinal vessels in rats with EIU were strongly positive for total prorenin, prorenin receptor, and activated prorenin. Systemic treatment with HRP resulted in dose- and time-dependent inhibition of the leukocyte adhesion and infiltration and the protein leakage, all of which were increased by the induction of EIU. Retinal mRNA expression and protein levels of ICAM-1, CCL2/MCP-1 and IL-6, induced in rats with EIU, were also significantly suppressed with application of HRP. CONCLUSIONS: These findings demonstrate for the first time that nonproteolytically activated prorenin plays a significant role in the development of ocular inflammation in the EIU model. The present study suggests the potential use of HRP, a decoy peptide binding to the prorenin receptor, as a therapeutic agent to reduce ocular inflammation.

Animals↗