[The study of new soft one-piece PHEMA keratoprosthesis implanted into alkali burned rabbits cornea].

OBJECTIVE: This study was to evaluate clinical results of two types soft one-piece keratoprosthesis (KPros) made of PHEMA implanted to alkali burned rabbit corneas. METHODS: Experimental study. Twelve pieces KPros were implanted alkali burned rabbit corneas(type I and II, 6 pieces respectively). The examinations including slit-lamp, fundus photography,B-ultrasound and ultrasound biomicroscopy (UBM) were carried out. RESULTS: All Kpros were stable and no complications happened including conjunctiva flap dehiscence, aqueous leak and infection. IOP were normal by finger touch. B-ultrasound show no retina detachment and UBM show synechia in most animals (10 case). Retroprosthetic membrane happened in type I (3 case) . Visible conjunctiva hyperplasia covering the optical region happened in all KPros. CONCLUSIONS: (1) The same material, integrated design, maybe eliminating the material interface problem. (2)Simple surgical skills. (3)IOP measurement is possible because of soft material. (4)KPro I do not need removal of the lens and vitrectomy. The projecting portion of KPro II may reduce the incidence of proliferative membrane. Long term effects need more cases and further observation.

[The expression level of MMP-2 and collagen of hydroxyapatite modified titanium for keratoprosthesis in the corneal stroma of rabbits].

OBJECTIVE: To investigate the expression level of metalloproteinases-2(MMP-2) and Collagen in a hydroxyapatite surfaced-modified of three Pan type titanium keratoprosthesis after that implanted into the corneal stroma of rabbits, further evaluate its biological compatibility. METHODS: Experimental study. Twenty-four New Zealand white rabbits, 2.0-2.5 kg, were respectively divided into three groups. Surgery was performed in right eye of all animals. skirt of HA-Ti and Ti were respectively inserted into the corneal stroma of rabbit of experimental group A and group B; only a sack was made without implantation in control group C . Cornea edema and corneal neovascularization were observed at scheduled times after operation; animals were sacrificed 2, 4 and 16 weeks after operation and their cornea was removed and examined under light microscopy; the surface of skirt was observed under scanning electron microscope. RESULTS: During the study period, all skirts were stable without infected, dissolved and excluded. Different degree of cornea edema and neovascularization was revealed after surgery. MMP-2 were absent in the normal corneal matrix. The expression level of MMP-2 in group A was higher than group C at all time points (F = 6.083, P < 0.05), and was increased than group B at 4th (F = 47.074, P < 0.01), and was increased than group C at 16th weeks too (F = 6.079, P < 0.05) . Corneal organization has a large green 4 weeks type III collagen and yellow red type I collagen, 16 weeks corneal mainly for bright red when within the collagen type I, still have a small amount of collagen type III. CONCLUSIONS: Rabbit cornea implanted HA-Ti skirts cause MMP-2 activation, continuous high expression didn't cause the cornea to dissolve; Collagen -III turned into collagen-I gradually in the extracellular matrix around the skirts. Hydroxyapatite modified titanium for Keratoprosthesis promoted the corneal neovascularization and improve the interfacial bio integration of skirt and host cornea.

[Biocompatible study of modified titanium skirt for keratoprosthesis].

OBJECTIVE: The research is engaged in developing an improved titanium skirt for keratoprosthesis, the aim of this study was to evaluate biocompatible of keratoprosthesis of novel design. METHODS: The pure titanium skirt for keratoprosthesis with three hands were first Sandblasted, and then bioactive hydroxyapatite coated on Sandblasted titanium for keratoprosthesis by a acid-alkali chemical treatment. A total of 18 New Zealand white rabbits and 18 alkali burned rabbit corneas were respectively divided into three groups (Group A, B and C; Group E, F and G) with simple random sampling methods. The modified titanium skirt was inserted into the corneal stroma of Group A and E, and then the control skirt was inserted into Group B and F. Group C and H did not insert skirt as surgery control. The interfacial biointegration of skirt/cornea were examined under light microscopy by HE, TEM and SEM. The transparent center was implanted to rabbit corneas with modified titanium skirt after 3 months. RESULTS: Dense hydroxyapatite coating was deposited on the Sandblasted specimens by an acid-alkali chemical treatment. The number of corneal fibroblasts increased significantly in Group A compared with Group B. The extracellular matrix deposited on the surface of modified titanium skirt was more dense and tight than that of control skirt. There was a significant difference in the shear force of skirt among groups A and B (t = 3.297, P < 0.05), E and F (t = 4.237, P < 0.05), and taking out the skirt in Group A and E were more difficulty than that in Group B and F after 3 months. The observation of the tissue sections of modified skirt inserted eyes revealed that there were cells and collagen-like fibres perpendicular to or at an angle to the rough interface and the cellular function was extremely active, in accordance with the results of TEM. Compared with healthy host tissue, skirt/cornea healing after alkali burn was impaired. CONCLUSIONS: Hydroxyapatite modified Sandblasted titanium skirt for keratoprosthesis can promote the interfacial biointegration of skirt and host cornea, no matter in healthy cornea or diseased cornea (alkali burn cornea). Hydroxyapatite coating improved the bioactivity of titanium.

J2 prolongs the corneal allograft survival through inhibition of the CD4+ T cell-mediated response in vivo.

In our previous report, we described a novel non-peptidic organic ligand of CD4 D1, designated J2, as a potential inhibitor of CD4 D1 and thus CD4-dependent T cell responses in vitro. In this work, we further used a murine model of corneal allograft rejection to determine its in vivo immunosuppressive activities. To mimic the situation in high-risk human eyes, the recipient mice corneas were all induced by intrastromal sutures to serve as neovascularized graft beds. J2 was administrated by mouth 3 h before transplantation and thereafter on consecutive 12 days. The results showed that J2 could significantly prolong the median survival time of the corneal allografts, compared to the untreated control group. And the subsequent functional assays, including T cell phenotype analysis, delayed-type hypersensitivity (DTH) and enzyme-linked immunospot (ELISPOT) assays revealed that the immunosuppressive activity of J2 was associated with its inhibitory effects on the CD4(+) T cells and these cells-mediated responses. All these results suggest that J2 is a potential lead for the development of new immunosuppressive agents to prevent the corneal allograft rejection.

[Biocompatibility of a special hydrogel orbital implant (PHEMA and MMA) in rabbits].

OBJECTIVE: To investigate the biocompatibility of a hydrogel orbital implant and its rate of vascularization in an experimental study. METHODS: The implant was made of copolymerization of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). Thirty-two hydrogel orbital implants were implanted into the right orbit of 32 New Zealand albino rabbits. The rate of vascularization was examined by SPECT, immunohistochemistry and electron microscopy. RESULTS: Single Positron Emission Computerized Tomography (SPECT) examination showed that a radiotracer could be found locally concentrated on hydrogel orbital implants in vivo along with time. On light microscopy, implants fibro vascular tissue invade the pores of the hydrogel orbital implant after 2 weeks and gradually invaded the implant deeper and deeper from 4 to 8 weeks, almost all implants were fully vascularized after 12 weeks with a relatively spare inflammatory reaction. Only one case needed additional surgery. CONCLUSIONS: The hydrogel orbital implant has many advantages, such as well biocompatible, fast vascularization, simple operation and low complication of surgery. It is safe and applicable for clinical use as a new type of orbital implant material.