scholarly journals Lipid accumulation and protein modifications of Bruch’s membrane in age-related macular degeneration

2021 ◽  
Vol 14 (5) ◽  
pp. 766-773
Author(s):  
Li-Hui Meng ◽  
Keyword(s):  
Macular Degeneration ◽  
Lipid Accumulation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Novel Therapy ◽  
Protein Modifications ◽  
Age Related

Age-related macular degeneration (AMD) is a progressive retinal disease, which is the leading cause of blindness in western countries. There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently. Until now, the pathogenesis of AMD has remained unclear, limiting the development of the novel therapy. Bruch's membrane (BM) goes through remarkable changes in AMD, playing a significant role during the disease course. The main aim of this review is to present the crucial processes that occur at the level of BM, with special consideration of the lipid accumulation and protein modifications. Besides, some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium (RPE) cells transplantation were listed. Hopefully, this review may provide a reference for researchers engaged in pathogenesis or management on AMD.

Bruch’s membrane pathology: A mechanistic perspective

2020 ◽  
Vol 30 (6) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aishwarya Murali ◽  
Subramanian Krishnakumar ◽  
Anuradha Subramanian ◽  
Sowmya Parameswaran
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Vital Role ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Age Related

Bruch’s membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch’s membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch’s membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch’s membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch’s membrane, which would aid in developing an effective therapy for these pathologies.

scholarly journals Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina

2019 ◽  
Vol 116 (47) ◽  
pp. 23724-23734 ◽  
Author(s):  
Shoji Notomi ◽  
Kenji Ishihara ◽  
Nikolaos E. Efstathiou ◽  
Jong-Jer Lee ◽  
Toshio Hisatomi ◽  
...  
Keyword(s):  
Basal Lamina ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Rpe Cells ◽  
Age Related ◽  
Deficient Mice

The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch’s membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD—namely, the accumulation of APOE, APOA1, clusterin, and vitronectin—adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch’s membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.

scholarly journals Saponin-Mediated Rejuvenation of Bruch’s Membrane: A New Strategy for Intervention in Dry Age-Related Macular Degeneration (AMD)

2021 ◽  
Author(s):  
Yunhee Lee ◽  
Eun Jung Ahn ◽  
Ali Hussain
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Age Related ◽  
New Strategy ◽  
The Matrix ◽  
Dry Amd ◽  
Underlying Mechanisms

At present, there is no treatment modality for the vast majority of patients with dry AMD. The pathophysiology of AMD is complex but current evidence suggests that abnormal ageing of Bruch’s membrane imparts a metabolic insult to the retinal pigment epithelium (RPE) and photoreceptor cells that leads eventually to the inflammatory-mediated death of these cells. Underlying mechanisms contributing to the pathology of Bruch’s membrane include the accumulation of ‘debris’ and malfunction of the matrix metalloproteinase (MMP) system resulting in diminished metabolic support of the retina and inefficient removal of toxic pro-inflammatory mediators. Saponins are amphipathic molecules that have a hydrophobic tri-terpenoid lipid region and hydrophilic glycosidic chains that allow for the dispersion of these deposits in Bruch’s and re-activation of the MMP system leading to a 2-fold improvement in the transport properties of the membrane. Such an intervention is expected to improve the bi-directional exchange of nutrients and waste products, thereby slowing the progression of dry AMD. This will be the first drug-based interventionist possibility to address dry AMD.

scholarly journals Morphological features of choroidal neovascular membranes in age-related macular degeneration complicated by high pigment epithelial detachment

2015 ◽  
Vol 96 (3) ◽  
pp. 364-368
Author(s):  
U R Altynbaev ◽  
O I Lebedeva
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Pigment Epithelial Detachment ◽  
Choroidal Neovascular Membrane ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Pigment Epithelial ◽  
Age Related

Aim. To study the morphological features of choroidal neovascular membranes in patients with wet age-related macular degeneration, complicated by high pigment epithelial detachment. Methods. The study enrolled 10 patients with wet age-related macular degeneration, who underwent vitrectomy with choroidal neovascular membranes removal, including 4 patients with occult choroidal neovascularization and 6 patients with classic choroidal neovascular membrane. Results. Histologic pattern consisting of pigmented epithelium cells layer with Bruch’s membrane, fibrovascular membrane, photoreceptors segments layer and, in some of the cases, choroid fragments, was discovered in tissue specimens of patients with classic choroidal neovascular membrane. Histologic pattern of choroidal neovascular membrane in patients with occult choroidal neovascularization also consisted of pigment epithelium cells layer with Bruch’s membrane, fibrotic neovascular membrane itself and photoreceptors segments layer. Pigment epithelium cell layer, in contrast to the control group, had apparent signs of hyperplasia. Average thickness of pigment layer of the retina was 16.08±4.64 μm in patients with high pigment epithelial detachment, by 30% higher compared to the control group (11.22±3.38 μm, р <0.05). Mean Bruch’s membrane thickness was 6.7±0.19 μm in the main group, which also exceeded the similar values in the control group (5.7±3.8 μm, р <0.05). Histochemical studies revealed qualitative differences between the study groups in the levels of collagen types I and III. Glycosaminoglycans, in contrast, were detected only in the group with classic choroidal neovascular membrane. Conclusion. In patients with occult choroidal neovascular membrane complicated by high pigment epithelial detachment, Bruch’s membrane thickening was found due to collagen type 1 deposits on the outer surface, which caused a local hydrodynamics alterations and influences the bioavailability of medications.

Tissue engineering of retina and Bruch’s membrane: a review of cells, materials and processes

2018 ◽  
Vol 102 (9) ◽  
pp. 1182-1187 ◽  
Author(s):  
Yong Sheng Edgar Tan ◽  
Pu Jiang Shi ◽  
Chang-J Choo ◽  
Augustinus Laude ◽  
Wai Yee Yeong
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Sheet ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Preclinical Model ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Cell Sheet Engineering ◽  
Age Related

The biological, structural and functional configuration of Bruch’s membrane (BM) is significantly relevant to age-related macular degeneration (AMD) and other chorioretinal diseases, and AMD is one of the leading causes of blindness in the elderly worldwide. The configuration may worsen along with the ageing of retinal pigment epithelium and BM that finally leads to AMD. Thus, the scaffold-based tissue-engineered retina provides an innovative alternative for retinal tissue repair. The cell and material requirements for retinal repair are discussed including cell sheet engineering, decellularised membrane and tissue-engineered membranes. Further, the challenges and potential in realising a whole tissue model construct for retinal regeneration are highlighted herein. This review article provides a framework for future development of tissue-engineered retina as a preclinical model and possible treatments for AMD.

Sign in / Sign up

Export Citation Format

Share Document