In vivo and in vitro investigations of retinal fluorophores in age-related macular degeneration by fluorescence lifetime imaging

2009 ◽  
Author(s):  
M. Hammer ◽  
S. Quick ◽  
M. Klemm ◽  
S. Schenke ◽  
N. Mata ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Fluorescence Lifetime ◽  
Age Related Macular Degeneration ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Age Related

scholarly journals Progressive dysmorphia of retinal pigment epithelium in age related macular degeneration revealed by fluorescence lifetime imaging

2021 ◽  
Author(s):  
Martin Hammer ◽  
Juliane Jakob-Girbig ◽  
Linda Schwanengel ◽  
Christine A. Curcio ◽  
Somar Hasan ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Fluorescence Lifetime ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Age Related

AbstractPurposeTo observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).MethodsMultimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization) (mean age: 74.2±7.0 years). Twenty-three eyes were followed for 28.3±18.3 months. Seven eyes had a second follow up after 46.6±9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, and migrated RPE, seen as hyperreflective foci (HRF) on OCT, were identified. Fluorescence lifetimes in two spectral channels (SSC: 500-560 nm, LSC: 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO.ResultsAs hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256±49 ps (SSC) and 336±35 ps (LSC) and an ESIR of 0.552±0.079. For hyperpigmentation, these values were 317±68 ps (p<0.001), 377±56 ps (p<0.001), and 0.609±0.081 (p=0.001), respectively, and for HRF 337±79 ps (p<0.001), 414±50 ps (p<0.001), and 0.654±0.075 (p<0.001).ConclusionsIn the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Experimental Models in Neovascular Age Related Macular Degeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4627
Author(s):  
Olivia Rastoin ◽  
Gilles Pagès ◽  
Maeva Dufies
Keyword(s):  
Macular Degeneration ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
In Vivo Models ◽  
Age Related ◽  
Decoy Receptors ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.

scholarly journals Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Majda Hadziahmetovic ◽  
Goldis Malek
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Clinical Care ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.

scholarly journals CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration

2020 ◽  
Vol 7 (5) ◽  
pp. 835-837 ◽  
Author(s):  
Changyang Zhou ◽  
Xinde Hu ◽  
Cheng Tang ◽  
Wenjia Liu ◽  
Shaoran Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Proof Of Concept ◽  
Rna Transcripts ◽  
Age Related ◽  
Rna Targeting

Summary RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration.

Two-dimensional fluorescence lifetime imaging for in-vitro and in-vivo application

1998 ◽  
Author(s):  
Paul M. W. French ◽  
Mark J. Dayel ◽  
Keith Dowling ◽  
Sam C. W. Hyde ◽  
M. J. Lever ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Fluorescence Lifetime Imaging ◽  
Two Dimensional ◽  
Lifetime Imaging
Sign in / Sign up

Export Citation Format

Share Document