Biomedical subjects

Yuichi Kaji

Publications and source records attributed to Yuichi Kaji.

At least 37 records · Page 2Linked to original sources

PubMed2004

Visualizing the vitreous body in the anterior chamber using 11-deoxycortisol after posterior capsule rupture in an animal model.

OBJECTIVE: To develop a new technique to visualize vitreous body prolapsed in the anterior chamber using 11-deoxycortisol. STUDY DESIGN: Experimental study. METHODS: An animal model of posterior capsule rupture was developed to investigate the usefulness of 11-deoxycortisol, a precursor of cortisol without steroid activity. After the intentional creation of posterior capsule rupture, the suspension of 11-deoxycortisol was injected into the anterior chamber of rabbit eyes. After gentle irrigation and aspiration, the vitreous body that had prolapsed into the anterior chamber was removed using an anterior vitrectomy cutter. To investigate the safety of 11-deoxycortisol, the biomicroscopic appearance, intraocular pressure (IOP), corneal endothelial count, and microstructure of the corneal endothelium were examined in the rabbits that received injections of 11-deoxycortisol in the anterior chamber. RESULTS: In our posterior capsule rupture model, the vitreous in the anterior chamber became clearly visible, with 11-deoxycortisol showing white particles entrapped on its surface. The injection of 11-deoxycortisol facilitated the complete removal of the vitreous body from the anterior chamber. In intact rabbit eyes, most of the injected 11-deoxycortisol had disappeared from the anterior chamber by 12 hours after injection. The injection of 11-deoxycortisol had no effect on IOP, corneal endothelial density, or the microstructure of the corneal endothelium. CONCLUSIONS: The injection of 11-deoxycortisol in the anterior chamber is useful in visualizing the vitreous body and has no significant side effects. This technique might reduce the intraoperative and postoperative complications of anterior vitrectomy after posterior capsule rupture.

Animals↗

PubMed2004

Correlations between allergen-specific IgE serum levels in patients with allergic conjunctivitis in spring.

PURPOSE: The purpose of this study was to evaluate the relation between various specific class E immunoglobulins (IgE) in serum and allergic conjunctivitis in spring. METHODS: Forty patients with allergic conjunctivitis and fifty healthy volunteers were selected for this trial. Total IgE and specific IgE to twelve inhalant allergens were measured using the CAP system. RESULTS: Specific IgE levels caused by cedar and cypress pollen, house dust, Dermatophagoides pteronyssinus, acarus, and moth allergens were higher in the allergy group than in the control group. No correlation was proven between the specific IgE levels and the total IgE level. The highest positivity rate for a specific allergen in patients with allergic conjunctivitis was 52.5% for cedar pollen, followed by cypress pollen at 37.5%. CONCLUSIONS: These results suggest that cypress pollen was the largest cause of allergic conjunctivitis and that the total IgE level had no correlation with each specific IgE.

Adult↗

PubMed2004

Potential use of (1,3)-beta-D-glucan as target of diagnosis and treatment of keratomycosis.

PURPOSE: Major problems in the management of keratomycosis stem from the difficulty of its diagnosis and limited choice of antifungal agents. In the present paper we propose a new method of detecting (1,3)-beta-D-glucan, one of the major components of fungal cell wall, in tears from an animal model of keratomycosis. In addition, we investigated the efficacy of topical application of micafungin, a new antifungal agent that inhibits the activity of (1,3)-beta-D-glucan synthase in this animal model. METHOD: Candida albicans (5 x 10(5) organisms) was inoculated into the corneal stroma of 20 New Zealand White rabbits. The animals were randomly assigned to two groups and treated with subconjunctival injection of 0.5 mL of saline or 0.1% micafungin every day for 3 weeks. The clinical course of keratomycosis in both groups was compared. Before and 3 weeks after the injection of saline or micafungin, 5 microL of tears in each eye were collected by capillary tube. The concentration of (1,3)-beta-D-glucan was quantitatively measured by modified Limulus test. RESULTS: The concentration of (1,3)-beta-D-glucan was significantly higher in keratomycosis model animals than in controls (mean +/- SD, 17.4 +/- 9.4 pg/mL and 2.8 +/- 1.8 pg/mL, respectively) at 21 days after treatment. Subconjunctival injection of micafungin had no significant effect on ocular lesions of keratomycosis until 9 days, after which ocular lesions significantly improved. Subconjunctival application of micafungin decreased the concentration of (1,3)-beta-D-glucan in tears to 4.9 +/- 3.0 pg/mL at 21 days after treatment. CONCLUSIONS: Increased levels of (1,3)-beta-D-glucan in tears were detected in this model of keratomycosis. Measuring the concentration of (1,3)-beta-D-glucan in tears may be a reliable noninvasive method for the diagnosis of keratomycosis. Topical application of micafungin was effective in the treatment of keratomycosis.

Animals↗

PubMed2004

Long-term changes in rabbit cornea after ionizing radiation.

PURPOSE: To investigate long-term changes in the cornea after ionizing irradiation in rabbits. METHODS: Mature albino rabbits (n = 4) were unilaterally irradiated with 20 Gy of x-rays. The contralateral eye served as a control. The rabbits were examined with slit-lamp biomicroscopy for 5 years. The eyes were then enucleated for histopathologic examinations with light microscopy and transmission electron microscopy. RESULTS: On biomicroscopy, there was no corneal abnormality during the 5-year follow-up period. On histopathology, no abnormality was observed in the corneal epithelium. In the endothelium, a vacuole-like structure was recognized by light microscopy, and transmission electron microscopy revealed marked enlargement of intercellular space and anamorphosis of the nuclei. CONCLUSION: Moderate x-ray irradiation to rabbit eye did not induce any long-term damage to the corneal epithelium, but the endothelium demonstrated persistent and irreversible damage, which was observed even 5 years after irradiation.

Animals↗

PubMed2004

VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2.

PURPOSE: Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, VEGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS: Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS: VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1 expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS: Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform and identify multiple mechanisms underlying its proinflammatory biology.

Animals↗

PubMed2003

VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization.

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.

Animals↗

PubMed2003

Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.

Animals↗

PubMed2003

Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown.

Platelet microthrombi are present in the diabetic retinal vasculature of humans and rodents; however, the mechanisms and consequences of their presence have not been defined. The current study demonstrates that platelet containing microthrombi accumulate in the retinal vasculature of the rat within 2 weeks of experimental diabetes, a timepoint at which leukocyte-mediated endothelial cell injury and death are known to occur. Platelet accumulation increased with the duration of diabetes, and crossover experiments revealed that maximal platelet accumulation required both diabetic platelets and a diabetic endothelium. Platelet accumulation also coincided with the expression of Fas and FasL in the diabetic retina. When endothelial cell apoptosis was inhibited with an anti-FasL neutralizing antibody, platelet accumulation was effectively suppressed. When platelets were depleted from the systemic circulation with an anti-platelet antibody, blood-retinal barrier breakdown worsened in the diabetic animals. These findings suggest that platelet accumulation in the diabetic retinal vasculature is secondary to endothelial cell death and serves, in part, to suppress blood-retinal barrier breakdown.

Animals↗

PubMed2003

Magnetic attraction of iron-endocytosed corneal endothelial cells to Descemet's membrane.

PURPOSE: To evaluate the feasibility of a novel method of magnetic attraction of iron-endocytosed corneal endothelial cells to Descemet's membrane. METHODS: Cultured rabbit corneal endothelial cells (RCEC) were exposed to spherical iron powder at various concentration ranging 0-100 micro moll(-1). After 24hr, the cell density and morphology were evaluated. RCEC that had been exposed to spherical iron powder (RCEC-iron), were trypsinized and poured onto a culture dish where a neodium magnet was fixated paracentrally. After 24hr, the cell density was measured at the areas with and without a magnet. Rabbits' corneas were cryo-injuried to detach corneal endothelial cells and 1x10(5)/200 micro l RCEC-iron were injected into the anterior chamber. Neogium magnet was fixed on the lid for 24hr to attract RCEC to Descemet's membrane. Each operated eye was observed up to 2 months after the injury. RCEC group (rabbits with cryo-injury and injection of normal cultured RCEC) and cryo group (rabbits with cryo-injury but without injection of RCEC) served as controls. RESULTS: The RCEC-iron density on the dish decreased in the medium containing iron powder of 10 micro moll(-1) or more. When RCEC had been exposed to iron powder of between 5 and 10 micro moll(-1), the ratio of RCEC in the field with a magnet to RCEC in the field without a magnet increased. In the RCEC-iron group, the mean corneal thickness gradually decreased and was significantly less than in the other two groups at 2, 4, and 8 weeks after the cell injection. Fluorescein microscopic examination showed a monolayer of DiI-labelled cells on the Descemet's membrane. CONCLUSION: Magnetic attachment of iron-endocytosed corneal endothelial cells to Descemet's nembrane can be a method of choice for corneal endothelial decompensation.

Animals↗

PubMed2003

Oculocardiac reflex caused by contact lenses.

PURPOSE: To report two cases of patients who fell unconscious because of the oculocardiac reflex when attempting to wear contact lenses. CASE REPORTS: Case 1: A 15-year-old healthy boy came to our clinic to be fitted with contact lenses. As soon as a hard contact lens was inserted forcibly, he became unconscious. Case 2: A 22-year-old man fell unconscious the instant that the eye was compressed with a hard contact lens. Neither patient had used glasses or contact lenses before. Their blood pressure was decreased while unconscious. They recovered consciousness after about 10 min, and nausea and vomiting settled subsequently. Contact lens insertion was tried again carefully after 1 week avoiding compression of the eyes and there were no problems. They are currently using contact lenses without any problems. CONCLUSION: Insertion of contact lenses may rarely provoke the oculocardiac reflex.

Adolescent↗

PubMed2003

Antigenicity of porcine cornea as xenograft.

PURPOSE: To investigate the antigenicity of porcine corneal stroma as xenograft to man. METHODS: The localization of alpha-gal epitope in the porcine eye was determined using biotinylated Griffonia simplicifolia 1 isolectin B4. Porcine corneal stromal was inserted into corneal stromal pockets of cynomolgus monkeys. Immunohistochemistry was performed to analyze the immunological reaction in the monkey. RESULTS: Immunohistochemistry showed no alpha-gal epitope in the porcine cornea except for several keratocytes in the anterior-most part. Haze and keratic precipitates developed in two corneas out of three corneas that were followed up until 6 months after the surgery. In these two corneas, infiltrating cells included CD4+, CD8+, or HAM56+ cells, suggesting that haze and keratic precipitates were induced by cellular rejection to porcine corneal stroma. CONCLUSIONS: Porcine corneal stroma induces no hyperacute rejection but mild cellular rejection when transplanted in the cornea of cynomolgus monkeys.

Animals↗

PubMed2003

Corneal wound healing after excimer laser keratectomy.

Excimer laser keratectomy is widely used to correct refractive errors. Several complications of excimer laser keratectomy are reported including corneal infection, regression, corneal haze formation, glare and halo. Most of the complications are closely related to the corneal stromal wound healing process. In order to perform the excimer laser keratectomy with minimum complications, we should understand the mechanism of the corneal stroma wound healing process. In addition, such knowledge will help us to regulate the corneal stromal wound healing process in the future. In the present article, we discuss the molecular mechanism of the corneal stromal wound healing process after excimer laser keratectomy and its regulation by anti-inflammatory agents.

Corneal Stroma↗

PubMed2003

Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells.

PURPOSE: The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death. METHODS: First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated. RESULTS: Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased. CONCLUSIONS: These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.

Animals↗

PubMed2003

VEGF164 is proinflammatory in the diabetic retina.

PURPOSE: The objectives of this study were to characterize the differential potency of two major VEGF isoforms, VEGF(120) and VEGF(164), for inducing leukocyte stasis (leukostasis) within the retinal vasculature and blood-retinal barrier (BRB) breakdown and to determine whether endogenous VEGF(164) mediates retinal leukostasis and BRB breakdown in early and established diabetes. METHODS: Retinal leukostasis and BRB breakdown were simultaneously quantified by combining concanavalin A lectin (ConA) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed to confirm that ConA-stained cells within the vasculature were leukocytes. Retinal leukostasis and BRB breakdown were compared in nondiabetic rats receiving intravitreous injections of VEGF(120) or VEGF(164). Retinal intercellular adhesion molecule (ICAM)-1 and VEGF protein levels were studied by Western blot and ELISA, respectively. An anti-VEGF(164(165)) aptamer (EYE001) was administered by intravitreous injection to 2-week and 3-month diabetic rats, and the effect on retinal leukostasis and BRB breakdown was quantified. RESULTS: Compared with VEGF(120), VEGF(164) more potently increased retinal ICAM-1 levels (2.2-fold), leukostasis (1.9-fold), and BRB breakdown (2.1-fold, P < 0.01 for all), despite negligible differences in vitreoretinal VEGF levels at the time of evaluation (P > 0.05). Retinal leukostasis and leakage increased with the duration of diabetes (P < 0.01) and correlated closely (P < 0.01, r = 0.889). The isoform-specific blockade of endogenous VEGF(164) with EYE001 resulted in a significant suppression of retinal leukostasis and BRB breakdown in both early (72.4% and 82.6%, respectively) and established (48.5% and 55.0%, respectively) diabetes (P < 0.01). CONCLUSIONS: On an equimolar basis, VEGF(164) is at least twice as potent as VEGF(120) at inducing ICAM-1-mediated retinal leukostasis and BRB breakdown in vivo. The inhibition of diabetic retinal leukostasis and BRB breakdown with EYE001 in early and established diabetes indicates that VEGF(164) is an important isoform in the pathogenesis of early diabetic retinopathy.

Animals↗

PubMed2003

The role of advanced glycation end products in retinal microvascular leukostasis.

PURPOSE: A critical event in the pathogenesis of diabetic retinopathy is the inappropriate adherence of leukocytes to the retinal capillaries. Advanced glycation end-products (AGEs) are known to play a role in chronic inflammatory processes, and the authors postulated that these adducts may play a role in promoting pathogenic increases in proinflammatory pathways within the retinal microvasculature. METHODS: Retinal microvascular endothelial cells (RMECs) were treated with glycoaldehyde-modified albumin (AGE-Alb) or unmodified albumin (Alb). NFkappaB DNA binding was measured by electromobility shift assay (EMSA) and quantified with an ELISA: In addition, the effect of AGEs on leukocyte adhesion to endothelial cell monolayers was investigated. Further studies were performed in an attempt to confirm that this was AGE-induced adhesion by co-incubation of AGE-treated cells with soluble receptor for AGE (sRAGE). Parallel in vivo studies of nondiabetic mice assessed the effect of intraperitoneal delivery of AGE-Alb on ICAM-1 mRNA expression, NFkappaB DNA-binding activity, leukostasis, and blood-retinal barrier breakdown. RESULTS: Treatment with AGE-Alb significantly enhanced the DNA-binding activity of NFkappaB (P = 0.0045) in retinal endothelial cells (RMECs) and increased the adhesion of leukocytes to RMEC monolayers (P = 0.04). The latter was significantly reduced by co-incubation with sRAGE (P < 0.01). Mice infused with AGE-Alb demonstrated a 1.8-fold increase in ICAM-1 mRNA when compared with control animals (P < 0.001, n = 20) as early as 48 hours, and this response remained for 7 days of treatment. Quantification of retinal NFkappaB demonstrated a threefold increase with AGE-Alb infusion in comparison to control levels (AGE Alb versus Alb, 0.23 vs. 0.076, P < 0.001, n = 10 mice). AGE-Alb treatment of mice also caused a significant increase in leukostasis in the retina (AGE-Alb versus Alb, 6.89 vs. 2.53, n = 12, P < 0.05) and a statistically significant increase in breakdown of the blood-retinal barrier (AGE Alb versus Alb, 8.2 vs. 1.6 n = 10, P < 0.001). CONCLUSIONS: AGEs caused upregulation of NFkappaB in the retinal microvascular endothelium and an AGE-specific increase in leukocyte adhesion in vitro was also observed. In addition, increased leukocyte adherence in vivo was demonstrated that was accompanied by blood-retinal barrier dysfunction. These findings add further evidence to the thinking that AGEs may play an important role in the pathogenesis of diabetic retinopathy.

Animals↗

PubMed2002

Inhibition of murine corneal allograft rejection by treatment with antibodies to CD80 and CD86.

The purpose of this study was to investigate the role of CD80 and CD86 costimulatory molecules in corneal allograft rejection. Anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) were administered after orthotopic corneal allograft transplantation. Graft rejection was observed by biomicroscopy. Population and localization of CD80(+)and CD86(+)cells in the cornea, cervical lymph nodes, and spleen were examined by flow cytometry and immunohistochemistry. The combined use of anti-CD80 and anti-CD86 mAbs was effective in prolonging corneal allograft survival. In the untreated mice bearing rejected graft, many CD86(+)and CD80(+)cells were found around the host-graft junctional area in the cornea, and CD86(high)cells were found in the cervical lymph node and spleen. In contrast, few CD86(+)or CD80(+)cells were observed in the cornea, cervical lymph node, and spleen from the mice treated with anti-CD80/CD86 mAbs. These results demonstrated a significant role of CD80 and CD86 costimulatory molecules in corneal allograft rejection.

Animals↗

PubMed2002

Spontaneous posterior dislocation of intraocular lenses fixated in the capsular bag.

We report 4 cases of complete posterior dislocation of an intraocular lens (IOL) in the capsular bag occurring a mean of 5.5 years after uneventful cataract surgery. In all 4 cases, posterior chamber IOLs were fixated within the capsulorhexis. The patients experienced sudden loss of vision without an episode of trauma or ocular disease. Using a 3-port pars plana vitrectomy, the IOLs were explanted through a limbal incision and a new IOL was sutured to the ciliary sulcus. Histological examination indicated that zonular fibers were severed at the site of insertion in the capsule.

Capsulorhexis↗

PubMed2002

The inflammatory milieu associated with conjunctivalized cornea and its alteration with IL-1 RA gene therapy.

PURPOSE: This study was designed to gain an insight into the inflammatory milieu into which a donor limbal graft is routinely introduced. The objective of this study was to modulate this environment by gene therapy with the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1 RA). METHODS: In a mouse model, the ocular surface cytokine environment associated with a conjunctivalized cornea was assessed 4 weeks after injury. Total corneal epithelial and limbal debridement was performed with a combination of alkali and scrape injury. The cytokines and adhesion molecules measured included IL-1alpha, IL-1beta, IL-6, VEGF, intercellular adhesion molecule (ICAM)-1, and vascular adhesion molecule (VCAM)-1, by real-time PCR or ELISA. Injured corneas were transfected with IL-1 RA by injection of naked plasmid vector pIRES-EGFP-IL-1 RA immediately after injury. Corneas transfected with pIRES-EGFP served as the control. Expression of corneal IL-1 RA after transfection with pIRES-EGFP-IL1-RA was assessed over a 2-week period by real-time PCR and Western blot analysis. In addition, limbal stem cell grafts transfected with IL-1 RA were assessed for leukocyte influx. RESULTS: Conjunctivalized corneas showed increased expression of IL-1alpha, IL-1beta, IL-1 RA, IL-6, VEGF, ICAM-1, and VCAM-1, compared with normal cornea. Transfection-efficiency experiments indicated that corneal expression of IL-1 RA peaked between 12 and 24 hours and lasted up to 2 weeks after the initial transfection. IL-1 RA corneal gene therapy resulted in a downregulation of IL-1beta and VCAM-1 expression at 4 weeks after injury, whereas downregulation of IL-6 was evident only at 1 week after injury. Corneal neovascularization was also reduced. In addition, corneal limbal stem cell grafts transfected with IL-1 RA showed a decreased leukocyte influx compared with control grafts. CONCLUSIONS: Transfection of a cornea with IL-1 RA immediately after epithelial injury selectively altered the cytokine profile of the resultant conjunctivalized cornea and suppressed corneal neovascularization. Transfection of corneal limbal donor tissue with IL-1 RA before engraftment can reduce leukocyte influx into the graft. The findings demonstrate the feasibility of using transient cytokine gene expression, either in donor or recipient corneal tissue, to alter the ocular surface environment beneficially.

Animals↗