SPARC-null Mice Exhibit Lower Intraocular Pressures

Haddadin, Ramez I.; Oh, Dong Jin; Kang, Min Gyu; Filippopoulos, Theodoros; Gupta, Meenakashi; Hart, Lawrence E.; Sage, E. Helene; Rhee, Douglas J.

doi:10.1167/iovs.08-2489

Cited by 67 publications

(100 citation statements)

References 45 publications

(42 reference statements)

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“…However, differences in collagen composition of the sclera may be correlated with suboptimal optic nerve head biomechanics, resulting in increased susceptibility to axonal damage in glaucomatous eyes. 66,67 The extracellular composition of the sclera is influenced and modified as a result of intraocular pressure fluctuations 68 and PACG-associated variants have also 73 Cong et al, 69 Wang et al, 70 Micheal 109 Chua et al, 104 Haddadin et al 110 …”

Section: Pacg Risk Factorsmentioning

confidence: 99%

“…108,109 SPARC-null mice reportedly display lower IOP than wild-type animals, which suggests a potential role for SPARC in regulating IOP. 110 Furthermore, investigation of two patient cohorts of Southern Chinese origin with acute and chronic PACG has led to the identification of an association between CALCRL polymorphisms and acute but not chronic PACG. 111 CALCRL (calcitonin receptor like) and related receptors are a family of G-protein-coupled receptors that comprise several subtypes.…”

Section: Nebmentioning

confidence: 99%

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The genetic mechanisms of primary angle closure glaucoma

Ahram

Alward

Kuehn

2015

Eye

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Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma affecting over 15 million individuals worldwide. Family history and ethnicity are strongly associated with the development of the disease, suggesting that one or more genetic factors contribute to PACG. Although strictly heritable disease-causing mutations have not been identified, a number of recent association studies have pointed out genetic factors that appear to contribute to an individual's risk to develop PACG. In addition, genetic factors have been identified that modify PACG endophenotypes for example, axial length. Herein we review the current literature on this important topic.

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Section: Pacg Risk Factorsmentioning

confidence: 99%

Section: Nebmentioning

confidence: 99%

The genetic mechanisms of primary angle closure glaucoma

Ahram

Alward

Kuehn

2015

Eye

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“…Intraocular pressures were recorded in both eyes of each animal with a handheld commercial rebound tonometer according to instructions by the manufacturer (TonoLab, Icare, Espoo, Finland). All measurements were taken between 4 and 7 min after anesthetic injection, as suggested by a prior study (20); 5 to 10 measurements of IOP in each eye were taken and the mean value of the IOP of the left operated eye is expressed as a percentage over that of the unoperated right eye of the same animal. An IOP that is < 70% of baseline IOP is used as an indicator of effective filtration and bleb function.…”

Section: Measurement Of Iopmentioning

confidence: 99%

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

Seet

Lee

et al. 2011

Mol Med

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“…Other groups have measured IOP in genetically modified mice lacking specific ECM molecules. This approach has identified SPARC, and thrombospondins-1 and -2 as having key roles in IOP regulation [19,20]. Perfusion of versican RNAi silencing lentivirus, or a recombinant HepII domain of fibronectin, has also implicated versican and fibronectin [48,57,58].…”

Section: Regulation Of Aqueous Humor Outflow Resistancementioning

confidence: 99%

“…These particular matricellular proteins are also expressed in the JCT of the TM and their function in IOP regulation is just beginning to be realized. Measurement of IOPs in these knockout mice has shown that genetic ablation of some matricellular genes exhibit lower IOPs (TSP-1, TSP-2, SPARC) [19,20], while for others there is no significant effect on IOP (hevin, osteopontin, tenascin C, tenascin X) [21,22,32]. What one will notice is that there seems to be an intriguing commonality between these groups of molecules and the two biological processes ( Table 1): molecules that do not contribute to IOP regulation are ones that are expressed during the inflammatory phase of the FBR (hevin, OPN), while ablation of molecules that affect IOP are those that are involved in capsule formation during the FBR (SPARC, TSP-1, TSP-2).…”

mentioning

confidence: 99%

The Juxtacanalicular Region of Ocular Trabecular Meshwork: A Tissue with a Unique Extracellular Matrix and Specialized Function

2013

J Ocul Biol

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The trabecular meshwork (TM) is a filter-like tissue located in the anterior segment of the eye. It is composed of a series of fenestrated beams through which aqueous humor flows to exit the anterior chamber via Schlemm's canal. The primary function of the TM is to regulate the flow of aqueous humor in order to establish intraocular pressure (IOP). Dysregulated aqueous humor outflow causes elevated IOP, which is a primary risk factor for glaucoma. The region of the TM implicated in establishing IOP lies adjacent to Schlemm's canal and is called the juxtacanalicular tissue (JCT) or cribriform region. Recent advanced light microscopy studies suggest that the JCT can be subdivided into inner and outer zones based on the localization of certain extracellular matrix (ECM) molecules. By comparing the ECM of the JCT to other connectives tissues and disease processes, this review outlines the evidence for two new concepts in TM biology: (1) continuous maintenance ECM remodeling, which may be critical in order to preserve open aqueous humor flow channels by releasing trapped debris and associated ECM fragments from the outflow pathways; (2) the JCT ECM as a barrier to functionally isolate the aqueous outflow channels. The ECM surrounding the outflow channels in the JCT may function to sequester small active regulatory molecules and prevent them from aberrantly modulating outflow resistance. These adaptations point to a distinctive tissue that has evolved transient ECM remodeling processes in order to regulate aqueous humor outflow and maintain rigorous control of IOP. KeywordsExtracellular matrix; Trabecular meshwork; Glaucoma; Outflow resistance; Intraocular pressure The Juxtacanalicular Trabecular MeshworkThe TM is a triangular-shaped tissue that is located in the scleral sulcus of the anterior chamber of the eye. The TM can be divided into separate regions based on anatomical location, which differ in both structure and function: the uveal and corneoscleral meshworks, the insert region, and the juxtacanalicular region (JCT) (Figure 1). The corneoscleral and uveal meshworks are comprised of fenestrated beams of lamellae, with large intertrabecular spaces between adjacent sheets [1]. These intertrabecular spaces decrease in size and the lamellae become slightly flatter as the corneoscleral meshwork transitions into the JCT region. The JCT is the deepest area of the tissue that lies adjacent to the inner wall (IW) endothelium of Schlemm's canal [2]. This area of tissue is approximately 2-20 μm thick. Unlike the uveal and corneoscleral meshworks, the JCT is not arranged into lamellae structures, but rather it is composed of a loosely arranged extracellular matrix (ECM) in which a sparse number of JCT cells are embedded [2]. These cells are separated from the IW endothelium, although they can extend processes that communicate with both IW cells and TM cells resident in the corneoscleral meshwork [3,4]. The ECM is highly hydrated and provides a conduit for aqueous humor to traverse the JCT and exit the anterior cham...

show abstract

SPARC-null Mice Exhibit Lower Intraocular Pressures

Abstract: SPARC-null mice have lower IOPs than do their WT counterparts with equal CCTs. The rate of aqueous turnover suggests that the mechanism is enhanced outflow resistance.

Cited by 67 publications

References 45 publications

The genetic mechanisms of primary angle closure glaucoma

The genetic mechanisms of primary angle closure glaucoma

Validation of the Glaucoma Filtration Surgical Mouse Model for Antifibrotic Drug Evaluation

The Juxtacanalicular Region of Ocular Trabecular Meshwork: A Tissue with a Unique Extracellular Matrix and Specialized Function

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