An in vivo model of focal light emitting diode-induced cone photoreceptor phototoxicity in adult pigmented mice: Protection with bFGF

Imperial-Ollero, Juan Antonio Miralles de; Gallego‐Ortega, Alejandro; Norte-Muñoz, María; Pierdomenico, Johnny Di; Valiente‐Soriano, Francisco J.; Vidal‐Sanz, Manuel

doi:10.1016/j.exer.2021.108746

Cited by 7 publications

(35 citation statements)

References 82 publications

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“…Focal phototoxic injury causes progressive S-cone loss within the lesioned area that has been recently described by our group both in rat [15] and mouse [15,18,33,34]. Our present studies in adult albino rat are somewhat similar to our previous studied by Ortín-Martínez et al (2014) [15].…”

Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationsupporting

confidence: 91%

“…This lesion progressed with time, producing a decrease in retinal thickness in the central part of the lesion, that was more marked in the outer retina. Although this alteration has been characterised in previous studies of both diffuse [22,33,34] and focal [15,18] blue LED phototoxic injury, our present work shows for the first time the effects over a long period of time, 30 days after LIP. Previous studies [24] have examined the effect of long-term ultraviolet LED focal damage on retinal thickness in pigmented C57Bl/6 mice, and although the exposure parameters were different, the authors report a similar retinal thinning with greater reduction of the outer retina from 2 to 12 weeks post-phototoxicity [24].…”

Section: Lip Induces a Focal Alteration In The Superior-temporal Retina Resulting In Thinning Of The Outer Retinal Layers Within The Lesisupporting

confidence: 42%

“…These cells reach the area of injury to activate immune resistance and modulated their morphology over time post-injury, from a more amoeboid-activated form, with a peak at 3 days, to a more branched-relaxed one [18]. This short-term effect has also been observed in a model of blue LED phototoxicity in pigmented mice [29,33]. However, this is the first study to analyse the long-term status of microglia following blue LED-induced phototoxicity.…”

Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationmentioning

confidence: 60%

“…Previous studies [24] have examined the effect of long-term ultraviolet LED focal damage on retinal thickness in pigmented C57Bl/6 mice, and although the exposure parameters were different, the authors report a similar retinal thinning with greater reduction of the outer retina from 2 to 12 weeks post-phototoxicity [24]. Thus, it is conceivable that the phototoxic focal lesion starts up a dynamic process that evolves with time, thereby making it an appropriate model for the study of neuroprotective therapies [15,18,33,34].…”

Section: Lip Induces a Focal Alteration In The Superior-temporal Retina Resulting In Thinning Of The Outer Retinal Layers Within The Lesimentioning

confidence: 99%

“…The present study shows the presence of autofluorescent material in the OS layer (yellow in Figure 2G-H') which is detected with both the green (488 nm) and red (564 nm) filters of the fluorescence microscope, and which starts to appear at 14 days after LIP and is more evident at 30 days. Previous studies have postulated that this autofluorescent material present in the OS layer may be derived from the oxidation of OS from photoreceptors which results in faster phagocytosis, and an accumulation of lipofuscin-like material [33]. This aggregation could interfere with their ability to remove cellular debris and may be one of the factors in the degenerative mechanism of overexposure to light.…”

Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationmentioning

confidence: 99%

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Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

Imperial-Ollero

Gallego‐Ortega

Norte-Muñoz

et al. 2021

IJMS

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Background: In adult rats we study the short- and long-term effects of focal blue light-emitting diode (LED)-induced phototoxicity (LIP) on retinal thickness and Iba-1+ activation. Methods: The left eyes of previously dark-adapted Sprague Dawley (SD) rats were photoexposed to a blue LED (20 s, 200 lux). In vivo longitudinal monitoring of retinal thickness, fundus images, and optical retinal sections was performed from 1 to 30 days (d) after LIP with SD-OCT. Ex vivo, we analysed the population of S-cone and Iba-1+ cells within a predetermined fixed-size circular area (PCA) centred on the lesion. Results: LIP resulted in a circular focal lesion readily identifiable in vivo by fundus examination, which showed within the PCAs a progressive thinning of the outer retinal layer, and a diminution of the S-cone population to 19% by 30 d. In parallel to S-cone loss, activated Iba-1+ cells delineated the lesioned area and acquired an ameboid morphology with peak expression at 3 d after LIP. Iba-1+ cells adopted a more relaxed-branched morphology at 7 d and by 14–30 d their morphology was fully branched. Conclusion: LIP caused a progressive reduction of the outer retina with loss of S cones and a parallel dynamic activation of microglial cells in the lesioned area.

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Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationsupporting

confidence: 91%

Section: Lip Induces a Focal Alteration In The Superior-temporal Retina Resulting In Thinning Of The Outer Retinal Layers Within The Lesisupporting

confidence: 42%

Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationmentioning

confidence: 60%

Section: Lip Induces a Focal Alteration In The Superior-temporal Retina Resulting In Thinning Of The Outer Retinal Layers Within The Lesimentioning

confidence: 99%

Section: Activation Of Iba-1 + Reactive Monocytic Cells In the Focal Area Of Injury Affecting The Cone Populationmentioning

confidence: 99%

See 3 more Smart Citations

Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

Imperial-Ollero

Gallego‐Ortega

Norte-Muñoz

et al. 2021

IJMS

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Intravitreal and subretinal syngeneic bone marrow mononuclear stem cell transplantation improves photoreceptor survival but does not ameliorate retinal function in two rat models of retinal degeneration

Pierdomenico

Gallego‐Ortega

Martínez-Vacas

et al. 2022

Acta Ophthalmologica

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To study and compare effects of syngeneic bone marrow mononuclear stem cells (BM-MNCs) transplants on inherited retinal degeneration in two animal models with different etiologies: the RCS and the P23H-1 rats. To compare the safety and efficacy of two methods of intraocular delivery: subretinal and/or intravitreal. Methods: A suspension of BM-MNCs was injected subretinally or intravitreally in the left eyes of P23H-1 and RCS rats at post-natal day (P) 21. At different survival intervals after the injection: 7, 15, 30 or 60 days, the retinas were crosssectioned, and photoreceptor survival and glial cell responses were investigated using immunodetection of cones (anti-cone arrestin), synaptic connections (anti-bassoon), microglia (anti-Iba-1), astrocytes and M€ uller cells (anti-GFAP). Electroretinographic function was also assessed longitudinally. Results: Intravitreal injections (IVIs) or subretinal injections (SRIs) of BM-MNCs did not produce adverse effects. The transplanted cells survived for up to 15 days but did not penetrate the retina. Both IVIs and SRIs increased photoreceptor survival, decreased synaptic degeneration and glial fibrillary acidic protein (GFAP) expression in M€ uller cells but did not modify microglial cell activation and migration or the electroretinographic responses. Conclusions: Intravitreal and subretinal syngeneic BM-MNCs transplantation decreases photoreceptor degeneration and shows anti-gliotic effects on M€ uller cells but does not ameliorate retinal function. Moreover, syngeneic BM-MNCs transplants are more effective than the xenotransplants of these cells. BM-MNC transplantation has potential therapeutic effects that merit further investigation.

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Minocycline Administration Does Not Have an Effect on Retinal Ganglion Cell Survival in a Murine Model of Ocular Hypertension

2024

Aging dis

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This study aims to investigate two key aspects in a mouse model of ocular hypertension (OHT): first, the time course of retinal ganglion cell (RGC) death and the parallel activation of caspase-3 (a-Casp3+ cells) to narrow the therapeutic window; and second, the effect of caspase-3 and microglia inhibition by minocycline on RGC rescue in this model. RGC loss after OHT induction was significant at day 7 and progressed to 30 days. However, anatomical RGC death was preceded by significant Casp3 activation on day 3. Microglial inhibition by minocycline did not alter the course of OHT or rescue RGCs but resulted in a decrease in a-Casp3+ cells and phagocytic and total microglia. Therefore, RGC death commitment occurs earlier than their loss of Brn3a expression, microglial cells do not exacerbate RGC loss, and while this death is primarily apoptotic, apoptosis inhibition does not rescue RGCs, suggesting that alternative death pathways play a role in glaucomatous injury.

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An in vivo model of focal light emitting diode-induced cone photoreceptor phototoxicity in adult pigmented mice: Protection with bFGF

Cited by 7 publications

References 82 publications

Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

Intravitreal and subretinal syngeneic bone marrow mononuclear stem cell transplantation improves photoreceptor survival but does not ameliorate retinal function in two rat models of retinal degeneration

Minocycline Administration Does Not Have an Effect on Retinal Ganglion Cell Survival in a Murine Model of Ocular Hypertension

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