Recent advances in ophthalmic molecular imaging

Carvalho, J. Emanuel Ramos de; Verbraak, Frank D.; Aalders, Maurice C. G.; Noorden, C. J. F. Van; Schlingemann, Reinier O.

doi:10.1016/j.survophthal.2013.09.005

Cited by 26 publications

(24 citation statements)

References 193 publications

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“…Apparent diffusion coefficient MRI has the potential to evaluate aspects of rod function complementary to that provided by manganeseenhanced MRI (MEMRI), the imaging modality of choice to study retinal calcium channels. 50,51 Combining these two methods is expected to provide useful complementary information if the presence of manganese does not somehow alter the ADC MRI measurement at the SRS layer. We thus tested, and confirmed, this possibility.…”

Section: Apparent Diffusion Coefficientmentioning

confidence: 99%

Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

Berkowitz

Grady

Khetarpal

et al. 2015

Investigative Ophthalmology & Visual Science

132

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Apparent diffusion coefficient MRI is a sensitive method for evaluating choroid thickness and its light-evoked expansion together with phototransduction-dependent changes in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast mechanism, its translational potential is promising; it can also be performed in concert with manganese-enhanced MRI (MEMRI). Our data support a link between diabetes-related oxidative stress and rod, but not choroidal, pathophysiology.

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Section: Apparent Diffusion Coefficientmentioning

confidence: 99%

Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

Berkowitz

Grady

Khetarpal

et al. 2015

Investigative Ophthalmology & Visual Science

132

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“…MEMRI, based on the activity-dependent Mn 2+ influx as a contrast agent that readily permeates cation channels but is much more slowly removed through intracellular clearance mechanisms, represents the imaging modality of choice for noninvasively mapping ion influx into ocular cells in vivo (25)(26)(27)(28). In vehicle-treated eyes, systemic (i.p.)…”

Section: Camentioning

confidence: 99%

Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels

Lakk

Frye

et al. 2016

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

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Fluid secretion by the ciliary body plays a critical and irreplaceable function in vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure. Here, we identify TRPV4 (transient receptor potential vanilloid isoform 4) channels as key osmosensors in nonpigmented epithelial (NPE) TRPV4 | ciliary body | intraocular pressure | aqueous humor | glaucoma F ormation of aqueous humor in the vertebrate eye takes place within the ciliary body (CB), a highly folded tissue consisting of pigmented epithelial (PE) cells, nonpigmented epithelial (NPE) cells, and the ciliary muscle (1, 2). Together, PE cells, which face the vascularized stroma and represent a forward continuation of the retinal pigment epithelium (RPE), and NPE cells, which face the posterior chamber (lumen) of the eye and extend the neuronal retina, form the blood-aqueous barrier and regulate the production and secretion of aqueous humor. The aqueous fluid supplies nutrients and oxygen to nonvascularized tissues (lens, cornea, and trabecular meshwork) and is ultimately drained through the ciliary muscle and the trabecular meshwork in the anterior chamber of the eye. Aqueous secretion is subserved by the unidirectional transport of ions and water through gap junctions between PE cells and NPE cells (3,4) and is driven by the osmotic gradient generated by Na + /K + exchange across basolateral NPE membranes (2-5). Despite the critical dependence of aqueous humor secretion on osmotic pressure (1, 4, 6), the molecular mechanism through which NPE and PE cells sense and regulate changes in volume is not well understood.In addition to osmotic shifts, CB cells experience mechanical forces associated with mean and time-varying aspects of intraocular pressure (IOP), a phenomenon that reflects balanced regulation of fluid secretion from NPE cells and its drainage from the anterior eye. Excessive IOP elevations represent the primary, and major, risk factor for contracting glaucoma (6, 7), an optic neuropathy that represents the second leading cause of blindness in the world. Therefore, aqueous secretion is often targeted by antiglaucoma medications that include β-adrenergic receptor antagonists, carbonic anhydrase inhibitors, α 2 -adrenergic agonists, and muscarinic cholinergic agonists (7). A key question, however, is whether CB cells themselves are able to sense force mediated by membrane stretch induced by hydrostatic pressure or swelling, and what such mechanisms might be.Here, we identify a key osmosensor in CB as transient receptor potential channel vanilloid isoform 4 (TRPV4), a polymodal nonselective cation-permeable channel that has been implicated in mechanotransduction (8, 9) as well as regulation of paracellular permeability in multiple epithelial tissues (10-15). Intriguingly, we found that TRPV4 is selectively distributed across CB by being confined to the NPE and excluded from PE cells. We characterized the functional role of TRPV4 as the predominant NPE swelling sensor and determined its contribution to...

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“…This represented an opportunity for a new approach to functional retinal imaging: combining Turnbulls' prolonged encoding of functional information with very high resolution images of the retina. MEMRI has been called the imaging modality of choice for non-invasively studying retinal ion homeostasis (Ramos de Carvalho et al, 2014). Much of the basic operational aspect of the MEMRI has been reviewed previously .…”

Section: Brief History Of Memrimentioning

confidence: 99%

MRI of rod cell compartment-specific function in disease and treatment in vivo

Berkowitz

Bissig

Roberts

2016

Progress in Retinal and Eye Research

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Rod cell oxidative stress is a major pathogenic factor in retinal disease, such as diabetic retinopathy (DR) and retinitis pigmentosa (RP). Personalized, non-destructive, and targeted treatment for these diseases remains elusive since current imaging methods cannot analytically measure treatment efficacy against rod cell compartment-specific oxidative stress in vivo. Over the last decade, novel MRI-based approaches that address this technology gap have been developed. This review summarizes progress in the development of MRI since 2006 that enables earlier evaluation of the impact of disease on rod cell compartment-specific function and the efficacy of anti-oxidant treatment than is currently possible with other methods. Most of the new assays of rod cell compartment-specific function are based on endogenous contrast mechanisms, and this is expected to facilitate their translation into patients with DR and RP, and other oxidative stress-based retinal diseases.

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Recent advances in ophthalmic molecular imaging

Cited by 26 publications

References 193 publications

Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy

Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels

MRI of rod cell compartment-specific function in disease and treatment in vivo

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