Autoimmune Dysregulation in Pigmentary Glaucoma
Condition: Pigmentary Glaucoma; Primary Open Angle Glaucoma; Cataract
MeSH terms: Glaucoma; Cataract; Glaucoma, Open-Angle
Study type: Interventional

Summary: 
      Based on these recent observations and findings in this new animal model of pigmentary
      glaucoma in the DBA/2J mouse, we propose that immune system abnormalities in the anterior
      chamber may play a possible role in the development of pigmentary glaucoma and possibly
      primary open-angle glaucoma (POAG) in humans.
    

Detailed description: 
      The aim is to establish, through tissue and aqueous analysis of patients with pigmentary
      glaucoma, POAG and normal controls, that markers for anterior chamber autoimmune dysfunction
      occur in significantly different amounts in patients with these conditions when compared to
      normal controls. We also will attempt to establish, through proven methodologies of tissue
      gene expression, that the source of these differences in markers, notably PEDF and IL-18, is
      from the uveal tissues of the anterior chamber, most importantly the iris and possibly the
      trabecular meshwork as well.

      The actual etiology at the cellular level of elevated intraocular pressure and the
      development of pigmentary glaucoma is not well understood in humans. If anterior chamber
      immune dysfunction were shown to be an important factor in the development of this disease in
      humans, which apparently is demonstrated by the DBA/2J mouse, it would lead to an important
      area of further investigation and possible novel approaches in treating or preventing this
      disease in humans.

      We hypothesize that in patients with pigmentary glaucoma, the amount of PEDF in the aqueous
      is significantly reduced while IL-18 is significantly elevated when compared to the aqueous
      of normal controls. In patients with POAG, we hypothesize similar results for PEDF, although
      significantly less reduction of PEDF when compared to the pigmentary glaucoma patients may be
      an interesting finding as well. With regard to IL-18, it is possible that amounts would be
      significantly elevated in the pigmentary glaucoma patients when compared to both normal
      controls and POAG patients. In view of the results from the DBA/2J mouse model, we hope to
      determine whether expression of PEDF could be down regulated in the iris and/or trabecular
      meshwork of pigmentary glaucoma patients when compared to POAG patients and whether IL-18
      expression in these tissues could be up regulated in pigmentary glaucoma patients when
      compared to POAG patients.

      Such findings would strongly suggest that anterior chamber immune abnormalities play a role
      in the etiology of pigmentary glaucoma in humans. It already has been suggested that
      decreased amounts and expression of PEDF are found in patients with glaucoma and other
      neurodegenerative diseases of the eye. However, the source of the decreased expression has
      not been identified. If IL-18 production is elevated in pigmentary glaucoma and is up
      regulated in the anterior chamber structures of the eye in human patients with the disease,
      this also would be highly suggestive that localized anterior chamber immune dysfunction plays
      a role in the development of this disease.

      Depending on our findings, additional investigations of autoimmune dysregulation in
      pigmentary glaucoma (and perhaps other secondary glaucomas) may help determine the predictive
      value of such markers in identifying whether or not patients with pigment dispersion syndrome
      develop glaucomatous damage.
    

Intervention name(s): Trabeculectomy; Trabeculectomy and cataract surgery; Cataract surgery
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): A surgical procedure used in the treatment of glaucoma to relieve intraocular pressure by removing part of the eye's trabecular meshwork; A surgical procedure used in the treatment of glaucoma to relieve intraocular pressure by removing part of the eye's trabecular meshwork and the removal of the cataract; Removal of the cataract from the eye
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: pigmentary glaucoma; primary open angle glaucoma; cataract; trabeculectomy; cataract surgery