The results demonstrated that RGC apoptosis in glaucoma correlates strongly with elevated IOP and is significantly associated with IOP-induced changes in specific ECM components in the RGC layer. The study shows for the first time a link between MMP-9, laminin degradation, RGC apoptosis, and IOP exposure in glaucoma. The findings suggest that abnormal ECM remodeling in the glaucomatous retina may relate to RGC death and support the notion that the retina is a primary site of injury in glaucoma.

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Purpose Clinical investigations have demonstrated variation in both the peak optical density and the spatial distribution of macular pigment. To confirm these impressions histologically, the present study examined the distribution of macular pigment in the human retina. Materials and Methods The macular retina of 11 donor eyes of different ages (28-91years) were examined histologically on 100 lm vibratome sections directly, without further staining. Measurements were made in two dimensions: (1) adding the number of macular sections with visible macular pigment, and (2) direct measurement of the extension of macular pigment in the foveolar section, which visibly contained the most macular pigment. Results The measurements with two methods demonstrated good correlation. The macula demonstrated a variation in the spatial extension of the visible macular pigment between 200 and 900 lm diameter around the centre of the fovea, which was also found when direct measurements were taken. There was no correlation with the donor age. The main location of macular pigment was in the layer of the fibres of Henle in the fovea and in the inner nuclear layer at the parafoveal site. Conclusions Histologically, a wide variation of the spatial distribution of macular pigment was found that confirms clinical observations. The primary localization of human macular pigment is in the inner retinal layers.

The scarring response is an important factor in many diseases throughout the body. In addition, it is a major problem in influencing results of surgery. In the eye, for example, post-operative scarring can determine the outcome of surgery. This is particularly the case in the blinding disease glaucoma, where several anti-scarring regimens are currently used to improve glaucoma surgery results, but are of limited use clinically because of severe complications. We have recently identified transforming growth factor-b (TGF-b) as a target for post-operative anti-scarring therapy in glaucoma, and now report the first study of novel secondgeneration antisense phosphorothioate oligonucleotides against TGF-b in vivo. Single applications of a TGF-b OGN at the time of surgery in two different animal models closely related to the surgical procedure performed in glaucoma patients, significantly reduced post-operative scarring (Po0.05) and improved surgical outcome. Our findings suggest that TGF-b antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring. Its long-lasting effects after only a single administration at the time of surgery make it particularly attractive clinically. Furthermore, although we have shown this agent to be useful in the eye, it could have widespread applications anywhere in the body where the wound-healing response requires modulation.

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