Jin-Jun Zhang

Safety and efficacy of intracapsular tranilast microspheres in experimental posterior capsule opacification

PURPOSE: To evaluate the safety and efficacy of a sustained‐release agent designed to reduce posterior capsule opacification (PCO). SETTING: Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, Peoples Republic of China. METHODS: Free tranilast (TFree) was incorporated into polylactic acid microspheres and then tested using a rabbit model of PCO. Twenty‐nine rabbits were randomized into 5 groups treated with balanced saline solution (BSS control); TFree; or 0.5, 1.0, or 2.0 mg tranilast microspheres (TMicro). Standard phacoemulsification cataract surgery, including manual aspiration of all visible soft lens matter, was performed in all groups. The selected test agent was then injected into the lens capsule. Postoperative clinical examinations were performed at 1, 3, 7, 14, 30, 60, and 90 days. Posterior capsule opacification was quantified using high‐resolution computer image analysis at 1, 2, and 3 months. Histological examination was performed at 3 months. RESULTS: Eyes treated with TMicro had significantly less PCO than the eyes in the BSS and TFree groups. While the BSS control eyes had increased PCO over 3 months, eyes in the TMicro group had reduced PCO over time in a dose‐dependent fashion. Histological examination showed reduced lens epithelial cell proliferation in the TMicro groups, with no manifest damage to the cornea, iris, or retina compared with the BSS controls. There was a transient increase in postoperative inflammation in all tranilast‐treated groups compared with the BSS controls. CONCLUSION: Sustained‐release intracapsular tranilast reduced PCO in an experimental model of PCO, suggesting further investigation of its therapeutic potential is justified.

In vitro lens capsule model for investigation of posterior capsule opacification.

&NA; A modified dissection technique of donor eyes for investigating posterior capsule opacification (PCO) that preserves normal capsule and zonule architecture is described. The intact crystalline lens–zonule–ciliary body complex is dissected from the globe in one piece and pinned with 8 entomological pins through the ciliary body to a soft silicone ring with an internal diameter of 12.7 mm. The specimen is iridectomized and cataract extraction performed; the specimen is then placed in culture. The capsule is supported by the native zonules and suspended freely within culture medium. The entire capsular bag is visible, allowing observation of lens epithelial cell (LEC) growth. In 15 eyes of 13 donors, the mean time to LEC confluence was 10.4 days ± 1.4 [SD]. This technique builds on previous capsular bag models, providing a more physiological model for observation of PCO in vitro. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Disturbed Matrix Metalloproteinase Pathway in Both Age-Related Macular Degeneration and Alzheimer's Disease

Purpose. Abnormal protein deposits including β-amyloid, found in ageing Bruchs membrane and brain, are susceptible to degradation by matrix metalloproteinases (MMPs). In ageing Bruchs membrane, these MMPs become less effective due to polymerisation and aggregation reactions (constituting the MMP Pathway), a situation much advanced in age-related macular degeneration (AMD). The likely presence of this MMP Pathway in brain with the potential to compromise the degradation of β-amyloid associated with Alzheimers disease (AD) has been investigated. Methods. Presence of high molecular weight MMP species (HMW1 and HMW2) together with the much larger aggregate termed LMMC was determined by standard zymographic techniques. Centrigugation and gel filtration techniques were used to separate and quantify the distribution between bound and free MMP species. Results. The MMP Pathway, initially identified in Bruchs membrane, was also present in brain tissue. The various MMP species displayed bound-free equilibrium and in AD samples, the amount of bound HMW1 and pro-MMP9 species was significantly reduced (p < 0.05). The abnormal operation of the MMP Pathway in AD served to reduce the degradation potential of the MMP system. Conclusion. The presence and abnormalities of the MMP Pathway in both brain and ocular tissues may therefore contribute to the anomalous deposits associated with AD and AMD.