Effective and Sustained Delivery of Hydrophobic Retinoids to Photoreceptors

Tang, Peter H.; Fan, Jie; Goletz, Patrice; Wheless, Lee; Crouch, Rosalie K.

doi:10.1167/iovs.10-5766

Cited by 25 publications

(45 citation statements)

References 28 publications

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“…9-cis-Retinaldehyde is effective with sustained delivery according to the study by Tang et al 41 Under dim red light, 20 mg/kg 9-cis retinaldehyde (Toronto Research Chemicals, ON, Canada) was dissolved in 20 lL of 100% ethanol and combined with 180 lL of Matrigel (vehicle; catalog number 356234, BD Bioscience, MA, USA) at 48C, as previously described. 41 In some mouse groups, vehicle with or without retinaldehyde was injected subcutaneously into the dorsal torso region several days prior to examination. Mice were then exposed to cyclic light for 2 days before being transferred to a dark room for 4 days per mouse.…”

Section: Treatmentsmentioning

confidence: 99%

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Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

Berkowitz

Kern

Bissig

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Diabetes appears to induce a visual cycle defect because rod dysfunction is correctable with systemic treatment of the visual cycle chromophore 11-cis-retinaldehyde. However, later studies have found no evidence for visual cycle impairment. Here, we further examined whether photoreceptor dysfunction is corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor dysfunction in diabetes, the hypothesis that exogenous visual chromophores have antioxidant activity in the retina of diabetic mice in vivo was tested.METHODS. Rod function in 2-month-old diabetic mice was evaluated using transretinal electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic tracking was used to evaluate cone-based visual performance. Retinal production of superoxide free radicals, generated mostly in rod cells, was biochemically measured with lucigenin. Diabetic mice were systemically treated with a single injection of either 11-cis-retinaldehyde, 9-cisretinaldehyde (a chromophore surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis-retinaldehyde).RESULTS. Consistent with previous reports, diabetes significantly reduced (1) dark-adapted rod photo responses (transretinal recording) by~18%, (2) rod-dominated light-stimulated SRS expansion (ADC MRI) by~21%, and (3) cone-dominated contrast sensitivity (using optokinetic tracking [OKT]) by~30%. Both 11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of photoreceptor dysfunction. Higher-than-normal retinal superoxide production in diabetes by~55% was also significantly corrected following treatment with 11-cis-retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde.CONCLUSIONS. Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction in diabetic mice, independent of the visual cycle, via an antioxidant mechanism.

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Section: Treatmentsmentioning

confidence: 99%

“…Mice were then exposed to cyclic light for 2 days before being transferred to a dark room for 4 days per mouse. 41 OKT or oxidative stress measurements were performed (strict 30-min examination per mouse, see below for details) on the fourth day.…”

Section: Treatmentsmentioning

confidence: 99%

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

Berkowitz

Kern

Bissig

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…In the Rpe65 −/− mouse, production of 11- cis RAL within the eye was undetectable, and a wave of cone death occurred within the first month of life [9]. Treating Rpe65 −/− mouse pups with exogenous 11- cis RAL immediately after birth rescued cones, reaffirming that an active visual cycle is essential for cone health [10]. …”

Section: Introductionmentioning

confidence: 99%

A subpopulation of activated retinal macrophages selectively migrated to regions of cone photoreceptor stress, but had limited effect on cone death in a mouse model for type 2 Leber congenital amaurosis

Tang

Heuss

Gregerson

2017

Molecular and Cellular Neuroscience

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Background Studies of antigen presentation in retina using mice that expressed green fluorescent protein (GFP) from a transgenic CD11c promoter found that retinal GFPhi cells possessed antigen presentation function. Subsequent studies found that these high GFPhi cells preferentially localized to sites of retinal injury, consistent with their APC function. Interest in the roles of macrophages in degenerative CNS diseases led us to study the GFPhi cells in a retinal model of neurodegeneration. We asked if apoptotic cone photoreceptor cell death in Rpe65−/− knockout mice induced the GFPhi cells, explored their relationship to resident microglia (MG), and tested their role in cone survival. Methods Rpe65−/− mice were bred to CD11cGFP mice on the B6/J background. CD11cGFPRpe65−/− mice were also backcrossed to CX3CR1YFP-creERROSADTA mice so that CX3CR1+ mononuclear cells could be depleted by Tamoxifen. Retinas were analyzed by immunohistochemistry, confocal microscopy, fluorescence fundoscopy and flow cytometry. Results Elevated numbers of GFPhi cells were concentrated in photoreceptor cell layers of CD11cGFPRpe65−/− mice coinciding with the peak of cone death at 2 to 4 weeks of age, and persisted for at least 14 months. After the initial wave of cone loss, a slow progressive loss of cones was found that continued to retain GFPhi cells in the outer retina. Sustained, four-week Tamoxifen depletions of the GFPhi cells and MG in Rpe65−/− mice from day 13 to day 41, and from day 390 to day 420 promoted a small increase in cone survival. We found no evidence that the GFPhi cells were recruited from the circulation; all data pointed to a MG origin. MG and GFPhi cells were well segregated in the dystrophic retina; GFPhi cells were foremost in the photoreceptor cell layer, while MG were concentrated in the inner retina. Conclusions The expression of GFP on a subset of retinal mononuclear cells in CD11cGFP mice identifies a distinct population of cells performing functions previously attributed to MG. Although GFPhi cells dominated the macrophage response to cone death in the photoreceptor cell layer, their ablation led to only an incremental increase in cone survival. The ability to identify, ablate, and isolate these cells will facilitate analysis of this activated, antigen-presenting subset of MG.

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“…The addition of Phyllanthus emblica extract can reduce retinal cells In the free radical content. in this way, Phyllanthus emblica extract can slow down the rate of apoptosis caused by mitochondrial disintegration, and can reduce the retinal cells due to excessive free radical content and damage, and then to achieve effectiveness of protection of retinal cells, and to achieve eye care effect [7,12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Phyllanthus emblica extract products can be used as an additive enhance the flavor making it easy to eat [13].…”

Section: Discussionmentioning

confidence: 99%

Food Supplements Were Applied to the Mitochondrial Capacity of Retinal Cells and Oxidative Phosphorylation of Adenosine Triphosphate (ATP) Synthesis

Yang¹,

Tu²,

Cheng³

et al. 2017

JFNR

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The retina consists of many different cells, the most important of which are retinal cells. Retinal cells have a lot of mitochondria. The mitochondria in retinal cells provide the energy of retinal cell activity, including the energy required to convert light into nerve signals. However, when the sun enters the eye and is irradiated on the retina, the high-energy ultraviolet light in the solar energy causes the mitochondria in the retinal cells and retinal cells to produce free radicals. These free radicals are detrimental to retinal cells and mitochondrial intima. Long-term accumulation, in addition to free radicals directly to the damage caused by retinal cells, the serious damage to the mitochondrial intima can also cause mitochondrial decomposition, and then lead to retinal cell apoptosis. This study discloses an eye care method comprising the provision of Phyllanthus emblica extract for the use of retinal cells in the late stage of ultraviolet or ultraviolet irradiation to obtain mitochondria in retinal cells of chlorophyll extract for oxidative phosphoric acid (ATP) synthesis Higher than the mitochondria, without Phyllanthus emblica extract of retinal cells, and with triphosphate (ATP) for phosphorylation. According to the above method, the supply of Phyllanthus emblica extract retinal cells protects the inner membrane of mitochondria in retinal cells, thereby delaying the decomposition time of mitochondria, adding Phyllanthus emblica extract can also reduce the free radical content of retinal cells such as bamboo leaf extract can slow Mitotic decomposition caused by the rate of apoptosis and can reduce the effectiveness of retinal cells due to excessive free radical content and damage to protect retinal cells to achieve eye care.

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Effective and Sustained Delivery of Hydrophobic Retinoids to Photoreceptors

Cited by 25 publications

References 28 publications

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice

A subpopulation of activated retinal macrophages selectively migrated to regions of cone photoreceptor stress, but had limited effect on cone death in a mouse model for type 2 Leber congenital amaurosis

Food Supplements Were Applied to the Mitochondrial Capacity of Retinal Cells and Oxidative Phosphorylation of Adenosine Triphosphate (ATP) Synthesis

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