Mechanisms of Retinal Damage after Ocular Alkali Burns.

Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection.

Model studies on the formation of monochloropropanediols in the presence of lipase.

The formation of chloropropanols was investigated using model systems comprised of lipase, vegetable oil or fat, water, and sodium chloride. The results showed that measurable levels of the foodborne carcinogen 3-chloro-1,2-propanediol (3-MCPD) are formed in the presence of commercially available lipases of mammalian, vegetable, and fungal origins, incubated at temperatures of 40 degrees C. The highest yield of 3-MCPD was obtained in reaction mixtures containing lipase from Rhizopus oryzae, and all the lipases studied exhibited a high hydrolytic activity toward triglycerides from palm and peanut oil. In contrast, hydrolysis over time and the yield of 3-MCPD in olive and sunflower oils were significantly lower (up to 10-fold), possibly linked to the relatively lower amount (<18%) of saturated fatty acids in these oils. We provide here for the first time evidence that lipases are able to induce the formation of chloropropanols under model system conditions. However, the key intermediates and precise mechanistic aspects governing the formation of 3-MCPD in the presence of lipase still need to be elucidated.