Inhibitor of vascular endothelial growth factor receptor tyrosine kinase attenuates cellular proliferation and differentiation to mature neurons in the hippocampal dentate gyrus after transient forebrain ischemia in the adult rat.

Neurogenesis in the adult hippocampal dentate gyrus is promoted by transient forebrain ischemia. The mechanism responsible for this ischemia-induced neurogenesis, however, remains to be determined. It has been suggested that there may be a close relationship between neurogenesis and the expression of vascular endothelial growth factor, an angiogenic factor. The purpose of the present study was to examine the relationship between vascular endothelial growth factor and cell proliferation in the dentate gyrus after transient forebrain ischemia. The mRNA expression of vascular endothelial growth factor was increased in the dentate gyrus on day 1 after ischemia. Immunohistochemical analysis on day 9 after ischemia, when a significant increase in cell proliferation was seen, showed that the cerebral vessel space in the subgranular zone of the dentate gyrus had not been affected by the ischemia. Neither were the vascular densities on days 1 and 3 after ischemia altered compared with those of non-operated naïve control rats. Furthermore, the distance from the center of the proliferative cells to the nearest cerebral vessel of ischemic rats was comparable to that of the sham-operated rats. We demonstrated that transient forebrain ischemia-induced cell proliferation and differentiation to mature neurons in the hippocampal dentate gyrus was attenuated by the i.c.v. administration of a vascular endothelial growth factor receptor tyrosine kinase inhibitor. These results suggest that vascular endothelial growth factor receptor at the early period of reperfusion may contribute to neurogenesis rather than to angiogenesis in the hippocampal dentate gyrus.

Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens.

BACKGROUND AND OBJECTIVE: To study the mechanism of the reportedly low incidence of posterior capsule opacification (PCO) in eyes treated with a posterior chamber intraocular lens (PC IOL). MATERIALS AND METHODS: Various IOL designs, including the PC IOL, were studied using scanning electron microscopy. Rabbit lens capsules were studied histopathologically 2, 3, and 4 weeks after implantation of a PC IOL in one eye and a biconvex polymethylmethacrylate (PMMA) IOL in the contralateral eye as a control. RESULTS: The optic edge of the PC IOL was sharp and rectangular, whereas that of the biconvex PMMA or silicone IOLs from various manufacturers had been smoothed and rounded by polishing. PCO was significantly reduced in the eye with a PC IOL in all rabbits. The lens capsule wrapped tightly around the optic edge of the PC IOL so that it conformed to the same shape and thereby created a distinct rectangular bend in the capsule or a rectangle between the optic edge and the posterior capsule. Migrating lens epithelial cells (LECs) were obviously inhibited at that site. CONCLUSIONS: A discontinuous capsular bend or rectangle created by the sharp, square optic edge of the PC IOL may have induced contact inhibition to migrating LECs and reduced PCO. How, whether, and to what extent this design-dependent effect is influenced by features of the IOL material needs to be clarified by comparison with results achieved with an IOL made from the same material in a different design and vice versa.

Equator ring efficacy in maintaining capsular bag integrity and transparency after cataract removal in monkey eyes.

BACKGROUND: The purpose of the study was to evaluate the efficacy of the equator ring in maintaining capsular bag integrity at the equator and transparency of the posterior capsule after cataract surgery. using cynomolgus monkeys. METHODS: After lens removal using an infusion-aspiration method, a flexible silicone ring with a groove on its inner surface was inserted in the bag through a window made by continuous circular capsulorhexis in six eyes. Of these, four monkey eyes underwent posterior chamber intraocular lens (IOL) implantation and two monkey eyes did not receive IOLs. Lensectomy without ring insertion was performed as a control in the six fellow eyes. Of these, four eyes received an IOL and two did not. The eyes were followed for an average of 5.9 +/- 1.1 months before enucleation. The effects were evaluated by stereo and light microscopy. RESULTS: The ring effectively maintained the circular contour of the capsular bag (ratio of the short and long axes, 0.97 +/- 0.01) and posterior capsule transparency (P = 0.017). CONCLUSIONS: This study demonstrated that the equator ring is a promising device for maintaining capsular bag integrity and minimizing posterior capsule opacification after cataract surgery.

Explantation of endocapsular posterior chamber lens after spontaneous posterior dislocation.

The management of spontaneous posterior dislocation of an intraocular lens (IOL) (11.0 mm in overall diameter) encapsulated within the remaining lens capable is presented. The patient was a 55-year-old man who had had phacoemulsification following continuous curvilinear capsulotomy for monocular cataract 3 years earlier. The dislocated, encapsulated IOL was lifted up by hooking the fibrotic capsular opening with a bent disposable needle following vitrectomy and then explanted. A conventional posterior chamber lens with modified C-loops was inserted and sutured in the ciliary sulcus. This technique may be an alternative treatment for a posteriorly dislocated IOL. Histopathological examination clearly revealed that lens epithelial cell migration stopped at the planoconvex optic edge. This finding may be consistent with reports that the incidence of posterior capsule opacification with the planoconvex IOL is lower than with the bioconvex IOL.

Effect of intraocular sustained release of indomethacin on postoperative inflammation and posterior capsule opacification.

PURPOSE: To assess whether the sustained release of indomethacin significantly reduces postoperative inflammation and posterior capsule opacification (PCO). SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: A 7 mm diameter, 1 mm thick polylactic-polyglycolic acid disk containing 7 mg of indomethacin was implanted in five rabbit eyes after continuous curvilinear capsulorhexis and phacoemulsification. The disk and an IOL placed above it were implanted in the capsular bag. The contralateral eyes, which served as controls, received a disk without indomethacin and the same type IOL in the same manner. RESULTS: The indomethacin was fully released within 3 weeks in vitro, a release rate of about 14 micrograms/h. Postoperatively, aqueous flare intensity was significantly lower at days 2, 3, and 4 and at weeks 1, 2, and 3. Prostaglandin E2 was not detectable in the aqueous humor of the indomethacin-treated eyes on day 3 and at week 4. In the control eyes, mean concentration was 491 pg/ml +/- 54 (SD) and 990 +/- 243 pg/ml, respectively. Histopathological examination showed no significant decrease in PCO. CONCLUSION: Although sustained release of indomethacin significantly decreased inflammation, it did not reduce PCO.

Inhibition of migrating lens epithelial cells by sustained release of ethylenediaminetetraacetic acid.

PURPOSE: To evaluate the effect of the sustained-release of ethylenediaminetetraacetic acid (EDTA) chelating Ca++ on lens epithelial cell (LEC) migration. SETTING: Nishi Eye Hospital, Jinshikai Medical Foundation, Osaka, Japan. METHODS: Polylactic-glycolic acid disks containing 10% EDTA were placed in saline solution for about 2 weeks in vitro. About 60% (7 micrograms/hour) of the EDTA was released during that time. The disks with a posterior chamber intraocular lens placed above were implanted in the capsular bag in five rabbit eyes after continuous curvilinear capsulorhexis and phacoemulsification. A disk without EDTA and the same lens type were placed in the bag in the contralateral eyes, which served as controls. RESULTS: After 2 to 3 months, opacification in the central posterior capsule was significantly reduced in all eyes that received the disk with EDTA. CONCLUSION: The deprivation of Ca++ disrupted interaction between the posterior capsule and migrating LECs by inactivating the adhesion molecule integrin synthesized by LECs, significantly reducing LEC migration onto the posterior capsule.

Efficacy of equator rings in an experimental rabbit study.

OBJECTIVE: To determine the efficacy of the equator ring in maintaining the circular contour of the capsule bag equator and transparency of the posterior capsule after crystalline lens extraction in 12 rabbit eyes. METHODS: After phacoemulsification through a 5-mm window made by continuous circular capsulorrhexis in the central anterior capsule, a flexible silicone ring (outer diameter, 11.0 mm; width, 1.5 mm; and thickness, 1.5 mm) was implanted in the capsule in seven rabbit eyes. A 13.0-mm Sinskey-style posterior chamber intraocular lens was then implanted inside the ring. Three other eyes received only equator rings, and two others received only intraocular lenses. Eyes were followed up for 3.5 +/- 1.4 months (mean +/- SD) before enucleation and evaluation by stereomicroscopy; they then underwent light microscopic examination. RESULTS: The two eyes that received only the intraocular lens had equatorial distortion and severe posterior capsule opacification. In nine (90%) of the 10 eyes that were implanted with the rings, the circular contour of the equator was preserved, and seven (70%) of these 10 eyes had transparent posterior capsules. CONCLUSION: Implantation of the equator ring effectively maintained the circular contour of the capsule bag equator and inhibited cells at the bag equator from proliferating toward the center of the posterior capsule in the rabbit.

Complications associated with endocapsular balloon implantation in rabbit eyes.

After phacoemulsifying the lens in six rabbit eyes through a 1.3 mm anterior capsule opening, we implanted a silicone balloon in the capsular bag and filled it with liquid silicone. The eyes were enucleated nine to 21 months postoperatively, embedded in paraffin, stained with toluidine blue, and examined by stereoscopic and light microscopy. We looked at the postoperative complications primarily. All balloons were securely fixated within the capsule. Surface wrinkles were observed in two balloons. The injected silicone remained transparent. None of the lens capsules was completely transparent, although all remained relatively clear. Retrocorneal membranes were produced in one eye in which the silicone leaked.