The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology

Janssen, Sarah F.; Gorgels, Theo G. M. F.; Ramdas, Wishal D.; Klaver, Caroline C.W.; Duijn, Cornelia M. van; Jansonius, Nomdo M.; Bergen, Arthur A. B.

doi:10.1016/j.preteyeres.2013.09.001

Cited by 162 publications

(154 citation statements)

References 401 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…Given that the progressive RGC injury occurring in glaucoma is characterized by a multifactorial pathology putatively involving a host of excitotoxic, inflammatory, immune, vascular, biomechanical, and other factors [58][59][60], and that the mechanisms dictating RGC soma and RGC axon loss may be quite distinct [61][62][63], the epigenetic changes induced by RH-Post will likely be extensive in order to account for the magnitude of the protection achieved. It is also worth noting that, although exposures to intermittent systemic hypoxia may not ultimately be adopted as a clinical treatment for glaucoma patients, this very stimulus has established a strong record for protection against a variety of acute and chronic diseases in the CNS [27][28][29][30][64][65][66][67], and other tissues [68][69][70], and may not be easily mimicked by a pharmacologic, monotherapy approach.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

et al. 2015

View full text Add to dashboard Cite

The neuroprotective efficacy of adaptive epigenetics, wherein beneficial gene expression changes are induced by nonharmful "conditioning" stimuli, is now well established in several acute, preclinical central nervous system injury models. Recently, in a mouse model of glaucoma, we demonstrated retinal ganglion cell (RGC) protection by repetitively "preconditioning" with hypoxia prior to disease onset, indicating an epigenetic approach may also yield benefits in chronic neurodegenerative disease. Herein, we determined whether presenting the repetitive hypoxic stimulus after disease initiation [repetitive hypoxic "postconditioning" (RHPost)] could afford similar functional and morphologic protection against glaucomatous RGC injury. Chronic elevations in intraocular pressure (IOP) were induced unilaterally in adult male C57BL/6 mice by episcleral vein ligation. Mice were randomized to an RH-Post [1 h of systemic hypoxia (11 % oxygen) every other day, starting 4 days after IOP elevation] or an untreated control group. After 3 weeks of experimental glaucoma, the 21-27 % reduction and 5-25 % prolongation in flash visual-evoked potential amplitudes and latencies, respectively, and the 30 % impairment in visual acuity were robustly improved in RH-Post-treated mice, as was the 17 % loss in RGC soma number and 20 % reduction in axon integrity. These protective effects were observed without RH-Post affecting IOP. The present findings demonstrate that functional and morphologic protection of RGCs can be realized by stimulating epigenetic responses during the early stages of disease, and thus constitute a new conceptual approach to glaucoma therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

et al. 2015

View full text Add to dashboard Cite

show abstract

“…But clinically, "genetic glaucoma" pedigrees are not the norm (less than 5% of cases). Myocilin glaucoma accounts for less than 1.5 % of cases and it courses with high IOP [32]. In that case it could be classified as secondary glaucoma.…”

Section: Genetic Paradigmmentioning

confidence: 99%

Glaucoma as a Tax on Hominid Evolution. Constraints of the Experimental Animal Models of Glaucoma

Carreras¹

2016

J Clin Exp Ophthalmol

View full text Add to dashboard Cite

Glaucoma continues to be a mysterious disease. High intraocular pressure (IOP), once the landmark of the disease, has been relegated to the humble role of risk factor, despite the fact that lowering IOP continues to be the only partially successful treatment. Even with an IOP successfully controlled to statistical standards, many patients still mysteriously continue to progressively lose neural tissue. A novel pathogenetical mechanism has recently been put forward as the main agent of the disease. In this new light, some structural details of the human eye, the result of the peculiar evolutionary development, take on an unexpected role in the presentation of the disease. As results of cladistics analysis, the human eye appears as particularly prone to suffering glaucoma as a consequence of the evolutionary path taken. That makes glaucoma essentially a human (and related hominid) scourge. Exclusive features of the human eye compared to other vertebrates involve both the anterior and posterior segment. Those features that facilitate glaucoma in humans are absent in many of the purported animal models for the disease, and this inadequacy further convolutes the mystery of glaucoma. This suggests the division of the animal models into those that mimic the whole disease and those that only reproduce a pertinent histological feature. Unfortunately most animal models are based on high intraocular pressure which excludes most cases of low or moderate pressure. For any animal model, it is important the researcher accurately establishes the constraints of the model in order to avoid jumping to conclusions.

show abstract

“…Subsequently, under higher magnification, we further cut three blocks of 1 mm 3 , per eye, of the trabecular meshwork. Trabecular meshwork specimens were fixed with 2.5% glutaraldehyde for 4 hours, rinsed in 0.1M phosphate buffer pH 7.4 and post-fixed with 4% OsO 4 for 2 hours.…”

Section: Preparation Of Samplesmentioning

confidence: 99%

“…Risk of developing glaucoma is consistently greater with progressive high IOP. Other factors influencing glaucoma include age, ethnic group, genetic background, myopia, diabetes, migraine and vasospasm [3].…”

Section: Introductionmentioning

confidence: 99%

Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Vecino¹,

GaldósM²,

Bayón³

et al. 2015

J Cytol Histol

View full text Add to dashboard Cite

The elevation of intraocular pressure (IOP) can be caused by the obstruction of flow in the trabecular meshwork and the age of the individuals has been pointed as one risk factor influencing in developing glaucoma. This study was designed to elucidate the morphological and ultrastructural changes in the trabecular meshwork of young adult Göttingen minipigs eyes after experimentally inducing a moderated chronic elevation of intraocular pressure lasting for over 14 months. The method used was cauterization of episcleral veins, located post-trabecular in the flow pathway and thus not affecting the cells located in the trabecular meshwork. The tissue was analysed using electron microscopy in control and experimental eyes. An increase in the amount of fibrillar material in the subendothelial region with a decreased optically empty spaces and an increase in rough endoplasmic reticulum (rER) were observed in the young experimental eyes. By experimentally increasing the post-trabecular resistance to the aqueous outflow, the present study showed that IOP elevation led to ultrastructural changes and thus concluded that changes in the trabecular meshwork can take place not only due to the advanced age, but by mechanical action on the cells as well.

show abstract

The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology

Cited by 162 publications

References 401 publications

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

Glaucoma as a Tax on Hominid Evolution. Constraints of the Experimental Animal Models of Glaucoma

Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Contact Info

Product

Resources

About