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Purpose: Ceruloplasmin (Cp) expression is increased locally as a response to many neurodegenerative conditions. The purposes of this study were to confirm findings of Cp upregulation in glaucoma, detect the time course of this upregulation in a glaucoma model, and better localize its expression in the retina., Methods: mRNA and protein were extracted from the retina and brain of DBA/2 and C57BL/6 mice and were subjected to analysis by RT-PCR and immunoblotting. In addition, eyes from the same mouse strains were subjected to immunohistochemistry using antibodies specific for Cp. Eyes from human subjects with or without glaucoma were also subjected to immunohistochemical analysis for Cp., Results: Cp mRNA and Cp protein were upregulated in the retinas of glaucomatous DBA/2 mice. Upregulation of Cp occurred at approximately the time of extensive retinal ganglion cell (RGC) death and increased with increasing age to 15 months in the retinas but not in the brains of these animals. No age-related Cp upregulation was detected in the reference normal mouse strain (C57BL/6), which can develop significant nonglaucomatous RGC loss toward the end of the same time frame. Cp upregulation was also detected in most eyes from the patients with glaucoma. Cp upregulation was localized to the Müller cells within the retinas and in the area of the inner limiting membrane., Conclusions: Cp is upregulated in the retina of a commonly used glaucoma model (the DBA/2 mouse) and in most human glaucomatous eyes. The timing of this upregulation suggests that it may represent a reactive change of the retina in response to a noxious stimulus or to RGC death. Such Cp upregulation may represent a protective mechanism within the retina.

Purpose: To evaluate the safety and efficacy of postoperative verteporfin photodynamic treatment as an adjunct to glaucoma experimental filtration surgery in rabbits., Methods: Dutch belted (n = 15) rabbits underwent full thickness sclerectomy in one eye. The experimental group (group 1, n = 7) underwent i.v. injection of verteporfin and subsequent photoactivation at the operative site on postoperative day 1 (POD 1). Control groups of animals received either light exposure (group 2, n = 4) or verteporfin (group 3, n = 2), or no intervention (group 4, n = 2). Intraocular pressure (IOP) was measured prior to the procedure (POD 0) and daily thereafter for the first week after sclerectomy (PODs 1-7) and every other day for the second week (PODs 9, 11, 13, 15). Percentage IOP reductions of operated over contralateral control eyes were compared among the various groups. Success rates (percentage IOP reduction > 15%) were also compared between the experimental and control groups. Eyes were histologically examined for evaluation of fibrosis., Results: Rabbits in the experimental group (group 1) had a mean +/- SEM percentage IOP reduction of 25 +/- 3% during the follow-up period. In contrast, groups 2, 3 and 4 had IOP reductions of 4 +/- 5%, 12 +/- 7% and 4 +/- 6%, respectively (p < 0.005, anova among all four groups). Successful IOP reduction (> or = 15%) over the contralateral eye at POD 15 was achieved in six of seven experimental animals, but only in one of eight control animals (p < 0.02, chi-squared test). Bleb failure occurred significantly earlier in the control eyes compared with eyes receiving PDT (p < 0.003, log rank test). Blebs in the experimental group differed from those in the control groups histologically, lacking significant collagen deposition in the area of the sclerostomy., Conclusions: Wound healing in glaucoma surgery may be successfully modulated postoperatively using photodynamic therapy with i.v. administered photosensitizer.

Purpose: Complement has been implicated in the pathogenesis of neurodegenerative diseases. The purpose of this study was to investigate whether complement activation is part of the pathogenesis of retinal ganglion cell (RGC) loss in glaucoma., Methods: mRNA and protein was extracted from the retina and brain of DBA/2 and C57/BL6 mice and subjected to RT-PCR and immunoblot analysis, respectively. In addition, eyes from the same mouse strains were subjected to immunohistochemistry with antibodies specific to complement component 1q (C1q). Eyes from monkeys with unilateral experimental glaucoma were also subjected to immunohistochemical analysis, as were eyes from human subjects with or without glaucoma., Results: C1q mRNA and C1q protein were found to be upregulated in the retina of glaucomatous DBA/2 mice. Upregulation of C1q preceded the time of extensive RGC death and increased with increasing age to 15 months in the retina, but not in the brain. No age-related C1q upregulation was detected in the reference mouse strain (C57BL/6), which develops significant nonglaucomatous RGC loss toward the end of the same time frame. C1q upregulation was also detected in laser-induced glaucomatous monkey eyes and in some (but not all) eyes of patients with glaucoma. C1q upregulation was localized to the Müller cells within the retina and in the area of the inner limiting membrane., Conclusions: Complement expression is upregulated in the retina of two commonly used glaucoma models (in the DBA/2 mouse and the monkey) and in some human glaucomatous eyes. The timing of this upregulation suggests that complement activation plays a significant role in the pathogenesis of glaucoma.