Structural changes of the trabecular meshwork in different kinds of glaucoma

Tektas, Ozan-Yüksel; Lütjen–Drecoll, Elke

doi:10.1016/j.exer.2008.11.025

Cited by 306 publications

(262 citation statements)

References 26 publications

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“…Data have additionally demonstrated that contractile filaments in the TM cell cytoplasm exist, indicating that TM cells themselves may contract (12). Histologically, thickening of the trabecular beams and fusing of trabecular lamellae because of adhesions of the denuded portions of the trabeculae and accumulation of fibrillar plaque material in the juxtacanalicular tissue have been associated with POAG (13,14).…”

mentioning

confidence: 99%

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Zhu

Gramlich

Laboissonniere

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

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Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma. Transplantation led to significantly reduced IOP and improved aqueous humor outflow facility, which was sustained for at least 9 wk. The ability to maintain normal IOP engendered survival of retinal ganglion cells, whose loss is ultimately the cause for reduced vision in glaucoma. In vivo and in vitro analyses demonstrated higher TM cellularity in treated mice compared with littermate controls and indicated that this increase is primarily because of a proliferative response of endogenous TM cells. Thus, our study provides in vivo demonstration that regeneration of the glaucomatous TM is possible and points toward novel approaches in the treatment of this disease.G laucoma is one of the most common causes of irreversible vision loss and blindness worldwide; ∼60 million suffer from this disease, and of these, 7 million are blind (1). By definition all glaucoma involves some degree of vision loss, which is because of the death of retinal ganglion cells (RGC), as well as degeneration of the optic nerve head, the optic nerve, and the lateral geniculate nucleus (2, 3). Advanced age and elevated intraocular pressure (IOP) are the two most significant risk factors for the development of glaucoma. Elevated IOP is typically a result of disturbances in the balance of aqueous humor production and drainage. Aqueous humor is continuously synthesized within the eye and drained primarily through the trabecular meshwork (TM), a specialized structure located anterior to the root of the iris. Although occlusion of the aqueous humor outflow pathways can occur through several mechanisms, in the United States and other Western populations the most common form of glaucoma is primary open angle glaucoma (POAG), which manifests no gross abnormalities to the anterior portion of the eye.Randomized clinical trials have shown that reduction of IOP slows the onset and progression of glaucoma, even in patients without suspicious elevation of IOP (4, 5). Although there has been increasing awareness that factors other than elevated IOP contribute to glaucomatous damage, to date all treatments for glaucoma remain aimed at reducing IOP either through surgical or medical means, which has resulted in significant preservation of vision and increased quality of life for millions of glaucoma patients (6, 7).Although the TM in eyes with POAG appears relatively normal at a gross morphological level, a number of more subtle changes influencing the mechanical properties of the TM collage...

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mentioning

confidence: 99%

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Zhu

Gramlich

Laboissonniere

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

View full text Add to dashboard Cite

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“…This thickening, and presumably even stiffening, of the fibre sheaths prevents the collapse of the TM and Schlemm's canal with age. The observed increase in extracellular matrix in the outer TM may contribute to the increase in outflow resistance as seen in normal elderly eyes [27]. Furthermore, in previous studies the amount of sheath derived (SD)-plaques have been shown to be significantly greater in glaucomatous compared to normal age-matched eyes [8,33] suggesting that the excess of this material found in POAG eyes may also be responsible for the elevation of IOP.…”

Section: Discussionmentioning

confidence: 92%

“…It is further accepted that age related changes in the TM contribute to the development of elevated IOP, perhaps due to the impaired aqueous outflow resistance. Increased resistance to aqueous humor outflow, leading to the elevation of IOP, is a dominant risk factor for glaucoma [25,[27][28][29]. The structures responsible for such an increase include JCT and SC [30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Vecino¹,

GaldósM²,

Bayón³

et al. 2015

J Cytol Histol

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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.

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“…Visualizing the changes in the trabecular meshwork could yield more information about the pathophysiology in pigment dispersion, pseudo exfoliation, and perhaps even show changes due to corticosteroids in so-called high responders. 2,3 The SL SCAN-1 is a unique FD OCT system that can scan the posterior pole and anterior segment, and also the anterior chamber angle and the more peripheral retina. These four modalities combined into one device makes the SL SCAN-1 a very powerful aid in daily practice.…”

Section: Eyementioning

confidence: 99%

Scanning beyond the limits of standard OCT with a Fourier domain optical coherence tomography integrated into a slit lamp: the SL SCAN-1

Stehouwer

Verbraak

Vries

et al. 2010

Eye

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Purpose With a new Fourier domain optical coherence tomography (FD OCT) device, SL SCAN-1 (Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands), integrated into a slit-lamp OCT, scans can be obtained through a handheld lens. The necessary adjustment of the reference arm is possible by fast Z-alignment. This study was performed to prove the capability of SL SCAN-1 to scan through a three-mirror contact lens, scanning the peripheral retina and anterior chamber angle. Methods Different representative pathologies of the peripheral retina and anterior chamber were simultaneously observed and scanned with the SL SCAN-1. The scans of peripheral retinal lesions were obtained both through a handheld lens and through a three-mirror contact lens. The anterior chamber angle was scanned directly with the SL SCAN-1 in anterior mode, and through the gonio-mirror of a three-mirror contact lens with the SL SCAN-1 in posterior mode. Results OCT scans could be obtained with the SL SCAN-1 of the peripheral retina through both, a common handheld lens and a three-mirror contact lens. The scans obtained through a three-mirror contact lens were of better quality, visualizing details of the different layers of the retina more clearly. The scans of the anterior chamber, obtained through the gonio-mirror of a three-mirror contact lens, visualized the open anterior chamber angle, with details of fine structures.Conclusions The SL SCAN-1 is a unique FD OCT system, which is able to scan not only the posterior pole and anterior segment but also the anterior chamber angle and the more peripheral retina. These four modalities combined into one device could make the SL SCAN-1 a very powerful aid in daily practice.

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Structural changes of the trabecular meshwork in different kinds of glaucoma

Cited by 306 publications

References 26 publications

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Elevated Intraocular Pressure induces Ultrastructural Changes in the Trabecular Meshwork

Scanning beyond the limits of standard OCT with a Fourier domain optical coherence tomography integrated into a slit lamp: the SL SCAN-1

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