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

Abstract

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.

Genetically heterogeneous mice show age-related vision deficits not related to increased rod cell L-type calcium channel function in vivo

“…High resolution MRI of mouse retina is routinely performed in our laboratory (Berkowitz et al, 2016). All animals were maintained in darkness for at least 16 hrs before and during the dark-phase of the MRI examination.…”

“…After MnCl 2 injection, mice were maintained in the dark (or light) for another 3.5 to 4 hours. High resolution anatomical and apparent diffusion coefficient (ADC) data were acquired in the untreated mice on a 7 T system (Bruker ClinScan) using a receive-only surface coil (1.0 cm diameter) centered on the left eye; the presence of MnCl 2 does not alter ADC indices of light-evoked increases in water diffusion in the subretinal space (SRS) and in choroid thickness (Berkowitz et al, 2016;Berkowitz et al, 2015). The end of a fiber optic bundle was attached to a light source (Mark II Light Source; Prescott's Inc., Monument, CO) placed caudal to the eye, projecting at a white screen ∼1 cm from eye, similar to that previously described (Bissig and Berkowitz, 2012).…”

“…This method takes advantage of the fact that retinal uptake in vivo of the strong MRI contrast agent and calcium ion surrogate manganese (Mn 2+ ) occurs primarily via LTCCs (Berkowitz et al, 2016). In a typical experiment, animals are dark adapted to maximally open LTCCs in, for example, the photoreceptor layer, followed by a systemic injection of a nontoxic dose of MnCl 2 (Berkowitz et al, 2016).…”

“…This method takes advantage of the fact that retinal uptake in vivo of the strong MRI contrast agent and calcium ion surrogate manganese (Mn 2+ ) occurs primarily via LTCCs (Berkowitz et al, 2016). In a typical experiment, animals are dark adapted to maximally open LTCCs in, for example, the photoreceptor layer, followed by a systemic injection of a nontoxic dose of MnCl 2 (Berkowitz et al, 2016). The extent of retinal manganese uptake that occurs over the next four hours (while the animal is awake and freely moving) is then measured by MEMRI to assess the degree to which LTCCs were open (Berkowitz et al, 2016).…”

“…In a typical experiment, animals are dark adapted to maximally open LTCCs in, for example, the photoreceptor layer, followed by a systemic injection of a nontoxic dose of MnCl 2 (Berkowitz et al, 2016). The extent of retinal manganese uptake that occurs over the next four hours (while the animal is awake and freely moving) is then measured by MEMRI to assess the degree to which LTCCs were open (Berkowitz et al, 2016). Recently we implicated in vivo progressive, age-related increases in rod cell LTCC function in declining visual performance in 2-18 mo male Long-Evans rats (commonly considered an outbred rat strain) (Bissig et al, 2013).…”