The Ultrastructure of Bruch's Membrane

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit

“…Bruch's membrane is a laminated extracellular matrix located between the retinal pigmented epithelium (RPE) and the adjacent choriocapillaris and is composed of the RPE and choriocapillaris capillary basement membranes and associated collagen and elastin layers 362,363 . Bruch's membrane in rabbits is thinner than that of humans 364 . The RPE contain melanosomes, which lack melanin granules in albino rabbits such as the NZW strain.…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit

“…Bruch's membrane is a laminated extracellular matrix located between the retinal pigmented epithelium (RPE) and the adjacent choriocapillaris and is composed of the RPE and choriocapillaris capillary basement membranes and associated collagen and elastin layers 362,363 . Bruch's membrane in rabbits is thinner than that of humans 364 . The RPE contain melanosomes, which lack melanin granules in albino rabbits such as the NZW strain.…”

CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1)

“…Using healthy human Bruch’s membrane ex vivo, we demonstrated that mini-CR1 crosses Bruch’s membrane ( Fig 4 ); it is important to test this using human tissue because there is wide variation in Bruch’s membrane thickness and permeability between species. 39 The ability of an AMD therapeutic to cross Bruch’s membrane is now recognized as an important consideration for therapeutic design and delivery modality selection. 40 , 41 Bruch’s membrane acts as a selective barrier to many proteins, including complement proteins, based on size, hydrodynamic radius, and charge 17 , 42 ; if complement therapies are delivered to the vitreous humor or retina, failure to cross Bruch’s membrane may pose a significant barrier to realizing their full efficacy potential, because their function will be limited to retinal tissues and they will not treat complement overactivation in the choriocapillaris layer.…”

CTx001 for geographic atrophy: a gene therapy expressing soluble, truncated complement receptor 1 (mini-CR1)

“…Furthermore, we demonstrate that it inhibits MAC formation on the surface of CTx001 transduced ARPE19 cells and promotes C3b consumption in the cell culture media (Figure 6). Using human Bruch’s membrane ex-vivo , we demonstrated that mini-CR1 crosses Bruch’s membrane (Figure 4); it is important to test this using human tissue as there is wide variation in Bruch’s membrane thickness and permeability between species 38 . The ability of an AMD therapeutic to cross Bruch’s membrane is now recognised as an important consideration for therapeutic design and delivery modality selection 39,40 .…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit

“…Bruch's membrane is a laminated extracellular matrix located between the retinal pigmented epithelium (RPE) and the adjacent choriocapillaris and is composed of the RPE and choriocapillaris capillary basement membranes and associated collagen and elastin layers 362,363 . Bruch's membrane in rabbits is thinner than that of humans 364 . The RPE contain melanosomes, which lack melanin granules in albino rabbits such as the NZW strain.…”

CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1)

“…Using healthy human Bruch’s membrane ex vivo, we demonstrated that mini-CR1 crosses Bruch’s membrane ( Fig 4 ); it is important to test this using human tissue because there is wide variation in Bruch’s membrane thickness and permeability between species. 39 The ability of an AMD therapeutic to cross Bruch’s membrane is now recognized as an important consideration for therapeutic design and delivery modality selection. 40 , 41 Bruch’s membrane acts as a selective barrier to many proteins, including complement proteins, based on size, hydrodynamic radius, and charge 17 , 42 ; if complement therapies are delivered to the vitreous humor or retina, failure to cross Bruch’s membrane may pose a significant barrier to realizing their full efficacy potential, because their function will be limited to retinal tissues and they will not treat complement overactivation in the choriocapillaris layer.…”

CTx001 for geographic atrophy: a gene therapy expressing soluble, truncated complement receptor 1 (mini-CR1)

“…Furthermore, we demonstrate that it inhibits MAC formation on the surface of CTx001 transduced ARPE19 cells and promotes C3b consumption in the cell culture media (Figure 6). Using human Bruch’s membrane ex-vivo , we demonstrated that mini-CR1 crosses Bruch’s membrane (Figure 4); it is important to test this using human tissue as there is wide variation in Bruch’s membrane thickness and permeability between species 38 . The ability of an AMD therapeutic to cross Bruch’s membrane is now recognised as an important consideration for therapeutic design and delivery modality selection 39,40 .…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Rabbit

“…Bruch's membrane is a laminated extracellular matrix located between the retinal pigmented epithelium (RPE) and the adjacent choriocapillaris and is composed of the RPE and choriocapillaris capillary basement membranes and associated collagen and elastin layers 362,363 . Bruch's membrane in rabbits is thinner than that of humans 364 . The RPE contain melanosomes, which lack melanin granules in albino rabbits such as the NZW strain.…”

CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1)

“…Using healthy human Bruch’s membrane ex vivo, we demonstrated that mini-CR1 crosses Bruch’s membrane ( Fig 4 ); it is important to test this using human tissue because there is wide variation in Bruch’s membrane thickness and permeability between species. 39 The ability of an AMD therapeutic to cross Bruch’s membrane is now recognized as an important consideration for therapeutic design and delivery modality selection. 40 , 41 Bruch’s membrane acts as a selective barrier to many proteins, including complement proteins, based on size, hydrodynamic radius, and charge 17 , 42 ; if complement therapies are delivered to the vitreous humor or retina, failure to cross Bruch’s membrane may pose a significant barrier to realizing their full efficacy potential, because their function will be limited to retinal tissues and they will not treat complement overactivation in the choriocapillaris layer.…”

CTx001 for geographic atrophy: a gene therapy expressing soluble, truncated complement receptor 1 (mini-CR1)

“…Furthermore, we demonstrate that it inhibits MAC formation on the surface of CTx001 transduced ARPE19 cells and promotes C3b consumption in the cell culture media (Figure 6). Using human Bruch’s membrane ex-vivo , we demonstrated that mini-CR1 crosses Bruch’s membrane (Figure 4); it is important to test this using human tissue as there is wide variation in Bruch’s membrane thickness and permeability between species 38 . The ability of an AMD therapeutic to cross Bruch’s membrane is now recognised as an important consideration for therapeutic design and delivery modality selection 39,40 .…”