Table 1.
CYP1B1 mutations in primary congenital glaucoma (GCP).
Fig 1.
A: Pedigrees of congenital glaucoma families included in this study. CYP1B1 genotypes are indicated below the symbols. Arrows show probands. Blue symbols indicate glaucoma phenotypes. Carriers are denoted by black dots in symbols; +: wild-type allele. Genealogy PCG 49 has previously been reported [6, 24] B: Location in the polypeptide chain of the CYP1B1 mutations identified in the probands. Alpha-helix regions are indicated in green and indicated with capital letters (A’-K). βS: beta-sheet regions (blue box). The numbers above the scheme correspond to amino acid positions.
Fig 2.
Anterior-chamber angle of normal eyes.
A: Light micrograph. B and C: Transmission electron microscopy. B: Juxtacanalicular tissue (JCT) and corneoscleral trabecular meshwork (CTM). C: Uveal trabecular meshwork (UTM). A: The ciliary muscle (CM) is inserted backwards to the scleral spur (SP). Schlemm’s canal (SC) and the collector channel (CC) have an open lumen. The trabecular meshwork is constituted by well-developed trabecular beams (TB) and intertrabecular spaces (*). Two regions can be distinguished in the TM: the CTM, formed by 6 to 8 layers of trabecular beams and the UTM composed of 2 to 3 layers of trabecular beams. B and C: The JCT (in B) is composed by stellate cells (S) and a loose extracellular matrix in which collagen (C), elastic fibers (e), and numerous “optically empty spaces” (o) are visible. The trabecular beams both in CTM and UTM (in B and C) are constituted by a central core made up mainly by collagen (C), elastic-like fibers (e) and amorphous ground substance (G). This central core is coated by phagocytic endothelial cells (E) that can bridge the intertrabecular spaces (arrow). The main difference between CTM (in B) and UTM (in C) is the size of the intertrabecular spaces, being larger in UTM (b) than in CTM (a). [arrowhead: pigmented granules phagocyted].
Table 2.
Correlation of slit–lamp findings, histological-angle anomalies, and treatment in five patients with PCG and CYP1B1 mutations.
Fig 3.
Trabeculectomy sample from the right eye. A: Light micrograph. B-D: Transmission electron microscopy. A: Schlemm’s canal is absent. The region corresponding to the trabecular meshwork (TM) consists of a compact tissue. The ciliary muscle (CM) is located in front of the undifferentiated TM. B: Compacted trabecular beams (TB) (double arrows). Large endothelial cells (E) lining some of the trabeculae. Melanin granules (arrow). C: The image shows two trabecular beams fused (double arrows), the endothelial coating has disappeared at the point of fusion (asterisk). D: The trabecular core is filled by collagen (C) and elastic-like tissue (e). An enlarged endothelial cell (E) between two trabecular beams (TB) is shown. [double arrow: trabecular beam].
Fig 4.
Trabeculectomy sample from the right eye. A: Light micrographs. B-D: Transmission electron microscopy. A: Some remains of trabecular meshwork (TM) and an anterior ciliary vessel (arrow) are observed. No Schlemm’s canal or collector channels are visible. The ciliary muscle (CM) is inserted posterior to the trabecular meshwork (TM). Inset in A: Higher magnification of TM. B-D: In the area corresponding to the trabecular beams a compact tissue composed of abundant coalescent fibrillary collagen (C) and large amount of elastic-like fibers (e) is observed. The scarce endothelial cells lining the trabeculae show features of necrosis (arrowhead in C and D) and apoptosis (arrow in B). [SP: scleral spur].
Fig 5.
Trabeculectomy sample from the left eye. A: Light micrograph. B-G: Transmission electron microscopy. A: Schlemm’s canal (SC) has an open lumen. The corneoscleral trabecular meshwork (CTM) is constituted by quite compact trabecular beams. In the uveal trabecular meshwork (UTM) the intertrabecular spaces (b) are evident. B: The image shows a part of Schlemm’s canal (SC) and the juxtacanalicular tissue. In the SC, only debris of necrotic endothelial cells (N) is visible on a thick basal membrane (bm). In the juxtacanalicular tissue, alternate layers of elastic tissue (e), necrotic cells (N), fibrillary collagen (C) and abundant ground substance (G) are seen. C: The corneoscleral trabecular meshwork is constituted by a quite disintegrated tissue. The trabecular beams (TB) (double arrows) have an “empty” appearance and are separated by intertrabecular spaces filled with debris of necrotic endothelial cells (N) and detached collagen (C) from the trabecular beams. D: The image shows fused trabecular beams (TB) (double arrows) and in some zones between them, debris from necrotic cells (white arrowhead) appears. The trabecular beams is constituted by a basal membrane (bm), many elastic-like fibers (e), fibrillary collagen (C), and abundant ground substance (G). E: The image shows two endothelial cells, one shows necrosis (N) and the other one has autophagic activity (arrow). F and G: Detail of the autophagic activity of an endothelial trabecular cell. F: Mitophagy (mp). G: Autophagosome (ap) with a double-membrane containing cytoplasmic material and organelles: mitochondria (M), rough endoplasmic reticulum (RER) and ribosomes (R).
Fig 6.
Trabeculectomy sample from the left eye. Transmission electron microscopy. A: Uveal trabecular meshwork. B: High magnification of inset in A. The endothelial cells of the trabecular beams have disappeared and the remains are necrotic (N). In some areas, the trabecular beams have an empty appearance (white arrow) while others are completely filled (arrowhead) with type VI non-fibrillary collagen (nf) intermingled with the collagen of the basal membrane (bm), as observed in B. The degraded type VI collagen detaches from the periphery of the trabecular beam (black arrow). [e: elastic-like tissue; G: ground substance].
Fig 7.
Trabeculectomy sample from the left eye. Light micrographs. A: Schlemm’s canal (SC), juxtacanalicular tissue (JCT) (double arrows), corneoscleral trabecular meshwork (CTM) (double arrows) and uveoscleral trabecular meshwork (UTM) (double arrows) are shown. Intertrabecular spaces are evident in both the CTM (a) and UTM (b). The ciliary muscle (CM) is inserted overlapping the SC. Numerous red blood cells can be observed in all aqueous outflow pathways (arrowhead). B: High magnification of the image shown in A. The SC shows a large lumen. A well-defined light-blue band (arrow) is visible in the JCT (double arrows) next to the endothelial cells lining the inner wall of the SC. The CTM has evident intertrabecular spaces in some areas (a) while in others, the trabecular beams are fused (white double arrow).
Fig 8.
Trabeculectomy sample from the left eye. Transmission electron microscopy. A and B: Schlemm’s canal (SC), juxtacanalicular tissue (JCT) (double arrows), and corneoscleral trabecular meshwork (CTM) (double arrows). Some endothelial cells lining the inner wall of SC are necrotic (inset in A) and others have some vacuoles (inset in B). The JCT has two differentiated areas: a band (double white arrow) formed mainly by coalescent fibrillary collagen (C) with scarce “optically empty spaces” (o). Next to this band the second area is composed of fibrillary collagen (C), abundant elastic-like fibers (e), stellate cells (some of them necrotic) (S), and “optically empty spaces” (o). Most endothelial trabecular cells are necrotic (N). C: High magnification of the corneoscleral trabecular meshwork beams. The trabecular core is filled with coalescent fibrillary collagen (C), elastic-like fibers (e) and few “optically empty spaces” (o). The trabecular beams are lined by necrotic endothelial cells (N) lying on a basal membrane (bm) which is thickened in some areas. [a: intertrabecular spaces in CTM].
Fig 9.
Trabeculectomy sample from the left eye. A: Light micrographs. B-D: Transmission electron microscopy. A: Uveal trabecular meshwork. The intertrabecular spaces are open (b). Most of the trabecular endothelial cells have disappeared and those remaining are necrotic (N). Numerous red blood cells appear between the trabecular beams (arrowhead). B-D: High magnification of an uveal trabecular meshwork trabecular beam. B: Cross section. C and D: Longitudinal section. The trabecular core is filled with successive layers of collagen fibers (C) giving the appearance of onion-like layers. The collagen of the basal membrane (bm) is interspersed between successive layers of fibrillary collagen (C). In B-D necrotic remains of the endothelial cells lining the trabecular beams are observed (N). [e: elastic-like fibers; nf: non-fibrillary collagen VI].
Fig 10.
Trabeculectomy sample from the right eye. Light micrographs. A: Schlemm’s canal (SC) with an open lumen is present. The ciliary muscle (CM) is inserted posterior to the SC. B: The SC and two collector channels (CC) are observed. The intertrabecular spaces of the corneoscleral (a) trabecular meshwork (CTM) (double arrows) are less evident than those of the uveal (b) trabecular meshwork (UTM) (double arrows). C: Endothelial cells lining the SC wall (arrowhead). The arrow points to a giant vacuole. The juxtacanalicular tissue (JCT) (double arrows) is thick and composed of stellate cells (S), collagen fibers (C), and “optically empty spaces” (o). The CTM has a compact appearance although intertrabecular spaces (a) are visible. [E: trabecular endothelial cell].
Fig 11.
Trabeculectomy sample from the right eye. Transmission electron microscopy. A: Schlemm’s canal (SC). The endothelial cells lining the inner wall of SC have some giant vacuoles (arrow) and numerous caveolae (arrowhead). B: Juxtacanalicular tissue (JCT). The thick JCT is constituted by disorganized fibrillary collagen (C), abundant stellate cells (S), elastic-like fibers (e) and “optically empty spaces” (o). C: High magnification of the JCT shown in B.
Fig 12.
Trabeculectomy sample from the right eye. Transmission electron microscopy. A: corneoscleral trabecular meshwork (CTM). This region is made up of several layers of trabecular beams (TB) (double arrows) separated by small intertrabecular spaces (a). Numerous flat endothelial cells (E) line the TB. B: High magnification of a trabecular endothelial cell (E). Pinocytosis vesicles (arrowhead), dense bodies (d), and phagocytized melanin granules (M) are visible within endothelial cells. Rough endoplasmic reticulum (RER). C: High magnification of a trabecular beam of the corneoscleral trabecular meshwork. The trabecular beams are filled by abundant disorganized fibrillary collagen (C), elastic-like fibers (e) and electron-lucent ground substance (G). The basal membrane (bm) of the trabeculae endothelial cells is observed. Pinocytosis vesicles (arrowhead).
Fig 13.
Trabeculectomy sample from the right eye. A: Light micrograph. B and C: Transmission electron microscopy. A: The uveal trabecular meshwork is well differentiated. The intertrabecular spaces are open (b). Well-preserved endothelial cells (E) alternate with necrotic cells (N). B: Two uveal trabecular beams lined with well-preserved endothelial cells (E) and one necrotic cell (N). The trabecular beams are filled with abundant fibrillary collagen (C) and elastic-like fibers (e). C: High magnification of an uveal trabecular beam containing a large amount of disorganized coalescent fibrillary collagen. Cross-sectioned collagen fibers (TC) alternate with fibers sectioned longitudinally (LC). Scarce electron-lucent ground substance (G) between collagen fibers and elastic-like fibers (e) is visible. Debris of endothelial necrotic cells (N).