Clinical and Ocular Histopathological Findings in a Patient With Normal-Pressure Glaucoma

Abstract

To study the histopathological changes of eyes from a patient with normal-pressure glaucoma whose clinical and laboratory findings were well documented.Methods: Postmortem histopathological findings in a patient with normal-pressure glaucoma who had monoclonal gammopathy and serum immunoreactivity to retinal proteins were examined in comparison with those of an age-matched control subject. Clinicopathological correlations to laboratory findings were examined.Results: Clinical and histopathological findings of the patient, including cavernous degeneration of optic nerve and characteristic optic nerve cupping, were similar to those in patients with glaucoma who had high intraocular pressure. In addition, we found immunoglobulin G and immonuglobulin A deposition in the ganglion cells, inner and outer nuclear layers of the retina, and evidence of apoptotic retinal cell death using terminal deoxynucleotidyltransferasemediated deoxyuridine triphosphate nick end labeling technique.Conclusions: Serum antibodies to retinal proteins and retinal immunoglobulin deposition constitute novel findings in a patient with normal-pressure glaucoma and may contribute to better understanding of the mechanisms underlying glaucomatous optic neuropathy in this disorder.

Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

“…In addition, IOP is not elevated in all of the eyes exhibiting characteristics of glaucomatous neurodegeneration. Similar clinical (Tezel et al, 1996) and histopathological findings (Wax et al, 1998a) in glaucomatous eyes either with elevated or normal IOP indicate that there is also an IOP-independent component of neuronal damage in glaucoma. Considerable evidence mostly from blood flow studies has illustrated that besides IOP, tissue hypoxia is also associated with the pathogenic mechanisms underlying glaucomatous neurodegeneration.…”

“…Glaucomatous tissue remodeling involves prominent glial responses leading to alterations in extracellular matrix composition and distribution (Hernandez, 2000). Consistent with optic disc cupping and cavernous degeneration in glaucomatous eyes (Wax et al, 1998a), and as also supported by in vitro observations (Tezel et al, 2001a), tissue remodeling events in the glaucomatous optic nerve head preferentially result in tissue degradation, rather than scar tissue formation as detected in other types of optic nerve injuries. Such tissue degradation, despite glial activation and increased glial production of extracellular matrix molecules, has been associated with a parallel increase in the secretion of matrix metalloproteinases in glaucomatous eyes (Agapova et al, 2001;Yan et al, 2000).…”

“…Histopathological studies of glaucomatous human donor eyes (Kerrigan et al, 1997;Wax et al, 1998a) and experimental studies using different animal models of glaucoma have demonstrated that while optic nerve axons are progressively lost in glaucomatous eyes, RGCs die through apoptosis (Garcia-Valenzuela et al, 1995;Li et al, 1999;Quigley et al, 1995). As summarized in Figure 1, multiple pathogenic mechanisms triggered by elevated IOP and/or tissue hypoxia have been associated with optic nerve degeneration and RGC apoptosis in glaucoma.…”

Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental glaucoma

“…Although the triggers of RGC death are not clear, they have been shown to die by apoptosis in both animal models (4-6) and human disease (7,8). Activation of two initiator caspase pathways, caspase 8 (9, 10) and caspase 9 (5, 9), has been reported in experimental glaucoma.…”

Immune Modulation in Glaucoma – Can Manipulation of Microglial Activation Help?

“…There is an increased prevalence of monoclonal gammopathy (Wax et al, 1994), elevated serum titers of auto-antibodies to optic nerve head glycosaminoglycans , auto-antibodies to retinal antigen such as rhodopsin (Romano et al, 1995), small heat shock protein (Tezel et al, 1998;Tezel et al, 2004), glutathione S-transferase (Yang et al, 2001b), gamma-enolase (Maruyama et al, 2000) and phosphatidylserine (Kremmer et al, 2001). Immunoglobulin has also been detected in the glaucomatous retina (Wax et al, 1998a). Heat shock protein antibodies (e.g.…”