Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms

Lahola-Chomiak, Adrian; Walter, Michael A.

doi:10.1155/2018/5926906

Cited by 13 publications

(16 citation statements)

References 120 publications

(138 reference statements)

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“…In glaucoma, the role of complement in RGC synapse remodeling and monocyte infiltration has largely been investigated in the DBA/2J model 25,27,28 , which is a wellcharacterized model of disease that exhibits many similarities to human disease, including age-dependent progression and sectorial loss 93 . However, it is possible that such immune and/or inflammatory responses are influenced by the loss of function mutation in Gpnmb, which is expressed in myeloid cell lineages, as recently reviewed 94 .…”

Section: Complement Inhibition Restricts Onset and Progression Of Axomentioning

confidence: 99%

Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma

Bosco

Anderson

Breen

et al. 2018

Preprint

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Dysregulation of the complement system is implicated in neurodegeneration, including human and animal glaucoma. Optic nerve and retinal damage in glaucoma is preceded by local complement upregulation and activation, but whether targeting this early innate immune response could have therapeutic benefit remains undefined. Because complement signals through three pathways that intersect at complement C3 activation, here we targeted this step to restore complement balance in the glaucomatous retina, and to determine its contribution to degeneration onset and/or progression. To achieve this, we combined adeno-associated viral retinal gene therapy with the targeted C3 inhibitor CR2-Crry. We show that intravitreal injection of AAV2.CR2-Crry produced sustained Crry overexpression in the retina, and reduced deposition of the activation product complement C3d on retinal ganglion cells and the inner retina of DBA/2J mice.This resulted in neuroprotection of retinal ganglion cell axons and somata despite continued intraocular pressure elevation, suggesting a direct restriction of neurodegeneration onset and progression, and significant delay to terminal disease stages. Our study uncovers a damaging effect of complement C3 or downstream complement activation in glaucoma and establishes AAV2.CR2-Crry as a viable therapeutic strategy to target pathogenic C3-mediated complement activation in the glaucomatous retina.

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Section: Complement Inhibition Restricts Onset and Progression Of Axomentioning

confidence: 99%

Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma

Bosco

Anderson

Breen

et al. 2018

Preprint

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“…It is reported that it affects Caucasians more often than other races [1,9,11]. Many cases are sporadic; however, there are families with apparent autosomal dominant inheritance [12,13].…”

Section: Introductionmentioning

confidence: 99%

A case of dense pigment deposition of the posterior lens capsule

Trampuž¹

2020

BMC Ophthalmol

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Background Pigment dispersion syndrome (PDS) is a well-known entity which can lead to pigmentary glaucoma (PG). This case report presents a rare presentation of PG with bilateral dense pigment deposits of the posterior lens capsule. Case presentation A 72-year-old male came for his first appointment due to an asymmetric worsening of visual acuity. The examination showed unilaterally severely increased intraocular pressure, bilateral dense pigment deposition of the posterior lens capsule, and a shallow unilateral optic disk excavation. Gonioscopy revealed moderate pigmentation of the angle and a concave configuration of the peripheral iris in both eyes. The standard slit lamp examination showed no transillumination defects of either iris. Optical coherence tomography showed retinal nerve fiber layer (RNFL) thinning in the peripapillary and macular regions. An antiglaucoma medication was prescribed with a good lowering effect. Conclusion Pigment deposition of the posterior lens capsule, which has been rarely reported, is a possible important sign of PDS or PG.

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“…Pigmentary glaucoma is an important type of secondary open‐angle glaucoma (OAG) found in patients with the predisposing disease pigment dispersion syndrome (PDS). The development of pigmentary glaucoma from PDS is primarily attributed to sloughed pigment granules that deposit and accumulate in the trabecular meshwork, obstructing outflow . Traditionally, early treatment options have been similar to POAG with ocular hypotensive agents, although laser peripheral iridotomy has been suggested as an alternate first‐line treatment for pigmentary glaucoma intraocular pressure (PG IOP) elevation.…”

Section: Introductionmentioning

confidence: 99%

Trabecular micro‐bypass stent implantation with cataract extraction in pigmentary glaucoma

Ferguson

Ibach

Schweitzer

et al. 2019

Clinical Exper Ophthalmology

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Importance: Use of the trabecular micro-bypass stent with cataract surgery is well established to be safe and effective in primary open-angle glaucoma. This is the first study to exclusively evaluate use of the device in pigmentary glaucoma. Background: This study aimed to investigate the safety and efficacy of a trabecular micro-bypass stent in combination with cataract surgery in pigmentary glaucoma. Design: Retrospective, consecutive case series. Participants: Twenty-four eyes of 12 patients with pigmentary glaucoma implanted with one trabecular micro-bypass stent with concomitant cataract surgery. Methods: Baseline data was collected and compared to the following postoperative time points: 1 day, 1 week, 1 month out to 36 months (M36) after the procedure. Main Outcome Measures: These included intraocular pressure (IOP), number of glaucoma medications and need for additional surgery. Results: At M36 there was a 25% reduction in IOP to 14.68 ± 3.0 (P < .01) from 19.50 ± 6.7 mmHg at baseline. The mean number of glaucoma medications was 0.75 ± 1.0 prior to the surgery and 0.59 ± 0.6 (P > .05) at 36 M. At the 36 M time-point, 95% of eyes had IOP ≤ 18 mmHg and 68% of eyes were ≤ 15 mmHg. No eyes underwent a secondary glaucoma procedure. Conclusions and Relevance: The insertion of a single trabecular micro-bypass stent in combination with cataract surgery effectively provides a sustained reduction in IOP up to 3 years after surgery in patients with pigmentary glaucoma. The safety profile is favourable with low rate of IOP spikes and no patients requiring additional surgery. K E Y W O R D S iStent, MIGS, pigmentary glaucoma, secondary open-angle glaucoma, trabecular micro-bypass stent

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Molecular Genetics of Pigment Dispersion Syndrome and Pigmentary Glaucoma: New Insights into Mechanisms

Cited by 13 publications

References 120 publications

Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma

Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma

A case of dense pigment deposition of the posterior lens capsule

Trabecular micro‐bypass stent implantation with cataract extraction in pigmentary glaucoma

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