Ciliary blood flow and aqueous humor production

Kiel, Jeffrey W.; Hollingsworth, Michael A.; Rao, Reshma R.; Chen, M.; Reitsamer, Herbert A.

doi:10.1016/j.preteyeres.2010.08.001

Cited by 91 publications

(92 citation statements)

References 38 publications

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“…For example, adenosine modulates intraocular pressure (IOP) by modifying both inflow and outflow pathways of aqueous humor. Activation of A 3 adenosine receptors stimulates Cl − channels of nonpigmented ciliary epithelial cells, increasing inflow (Kiel et al, 2011) and IOP. Knockout of A 3 adenosine receptors lowers IOP (Avila et al, 2002).…”

Section: Recent Findings Regarding Purines In the Eyementioning

confidence: 99%

Purines in the eye: Recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

Sanderson

Dartt

Trinkaus‐Randall

et al. 2014

Experimental Eye Research

111

110

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This review highlights recent findings that describe how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca2+ concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease.

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Section: Recent Findings Regarding Purines In the Eyementioning

confidence: 99%

Purines in the eye: Recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

Sanderson

Dartt

Trinkaus‐Randall

et al. 2014

Experimental Eye Research

111

110

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“…Furthermore, it is also known that the avascular ocular tissues like the lens and the iris depend on aqueous humor for the nutrients and oxygen (Reitsamer and Kiel, 2003). Ultimately, ciliary circulation is responsible for the production and maintenance of aqueous humor through both the delivery of oxygen and nutrients, and the excretion of metabolic wastes (Kiel et al, 2011; Strauss, 2005). Hence, the more of vasculature, the more mitochondria-rich cells are needed to combat with the oxidative stress through a protective mechanism of Grx2.…”

Section: Discussionmentioning

confidence: 99%

Expression and distribution of thiol-regulating enzyme glutaredoxin 2 (GRX2) in porcine ocular tissues

Upadhyaya¹,

Tian²,

Wu³

et al. 2015

Experimental Eye Research

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Glutaredoxin2 (Grx2) is a mitochondrial isozyme of the cytosolic glutaredoxin1 (thioltransferase or TTase). Both belong to the large oxidoreductase family and play an important role in maintaining thiol/disulfide redox homeostasis in the cells. Grx2 is recently found in the lens where its activities of disulfide reductase and peroxidase, similar to TTase, can protect the lens against oxidative stress. Since other eye tissues are also highly sensitive to oxidative stress, and TTase’s distribution in the eye is known, we focused on this study by investigating the Grx2 distribution in the ocular tissues in comparison to the lens. Fresh porcine eyes were dissected into cornea, iris, ciliary body, the lens, vitreous humor, retina, and optic nerve. Each tissue (pooled from three eyes) was homogenized and processed for mitochondrial isolation. The mitochondrial fraction was analyzed for Grx2 protein using Western blotting with anti-Grx2 antibody, and Grx2 activity using the published procedure. The eye tissues were also measured for Grx2 mRNA expression by RT-PCR with GAPDH as the control. Grx2-rich mouse liver and purified recombinant mouse Grx2 were used as positive controls for the above analyses. It was found that Grx2 was present in all the tested ocular tissues, except vitreous humor. In comparison with the mouse liver, the protein levels of Grx2 in porcine ciliary body and the lens were 27-fold and 0.75-fold, respectively. Comparing to the lens, Grx2 protein was highest in the ciliary body (13.5-fold), followed by retina (9.2-fold), iris and optic nerve (2-fold), and cornea (1.2-fold). Enzyme activity assays showed that the retina had the highest Grx2 specific activity (3.9 mU/mg protein), followed by ciliary body (3.1 mU/mg), the lens (0.58 mU/mg), and optic nerve (0.32 mU/mg). Grx2 gene expression in these ocular tissues was further confirmed by RT-PCR analysis. Grx2 mRNA expression showed the highest in ciliary body, followed by retina, optic nerve, cornea, iris, and the lens. No Grx2 mRNA, protein or enzyme activity could be found in the vitreous humor. The results indicate that Grx2 level was higher in eye tissues rich in vasculature and mitochondria (i.e. ciliary body and retina), corroborating with the levels of mRNA expression and Grx2 activity. The rich presence of Grx2 in these tissues is also consistent with their known sensitivity to oxidative stress.

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“…[7][8][9][10] Parameters such as the aqueous viscosity and the iris stiffness and thickness will be dependent on the pathology of the disease and these values can only be estimated.…”

Section: Optimum Size Of Iridotomy In Uveitismentioning

confidence: 99%