Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

Souma, Tomokazu; Tompson, Stuart W; Thomson, Benjamin R.; Siggs, Owen M.; Kizhatil, Krishnakumar; Yamaguchi, Shinjiro; Li, Feng; Limviphuvadh, Vachiranee; Whisenhunt, Kristina N; Maurer‐Stroh, Sebastian; Yanovitch, Tammy L.; Kalaydjieva, Luba; Azmanov, Dimitar N.; Finzi, Simone; Mauri, Lucia; Javadiyan, Shahrbanou; Souzeau, Emmanuelle; Zhou, Tiger; Hewitt, Alex W.; Kloss, Bethany A Volkmann; Burdon, Kathryn P.; Mackey, David A.; Allen, Keri; Ruddle, Jonathan B; Lim, Sing Hui; Rozen, Steve; Tran-Viet, Khanh-Nhat; Liu, Xiaorong; John, Simon W. M.; Wiggs, Janey L.; Pasutto, Francesca; Craig, Jamie E; Jin, Jing; Quaggin, Susan E.; Young, Terri L.

doi:10.1172/jci85830

Cited by 203 publications

(230 citation statements)

References 63 publications

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“…This phenotype is replicated in mice lacking the angiopoietin receptor TEK, confirming that signaling through the classical angiopoietin/TEK signaling axis is essential for SC formation (7,8). However, while the importance of TEK signaling is clear, specific roles for each angiopoietin ligand have not been previously described.…”

Section: Discussionmentioning

confidence: 71%

“…Similarly, Angpt1 WBΔE16.5 mice exhibited a severely hypoplastic SC phenotype characterized by gaps and discontinuous, isolated canal segments. While this phenotype was less severe than in the SC endothelium (5), have been identified in patients with primary congenital glaucoma (PCG), an especially devastating form of the disease characterized by infant/early-childhood onset, buphthalmos, and optic neuropathy (8). In mice, loss of TEK signaling through either deletion of both primary ANGPT ligands or deletion of the TEK receptor results in failure of SC development and rapidly progressing ocular hypertension (7,8).…”

Section: Angpt1 and Angpt2 Are Expressed In The Iridocorneal Anglementioning

confidence: 99%

“…While this phenotype was less severe than in the SC endothelium (5), have been identified in patients with primary congenital glaucoma (PCG), an especially devastating form of the disease characterized by infant/early-childhood onset, buphthalmos, and optic neuropathy (8). In mice, loss of TEK signaling through either deletion of both primary ANGPT ligands or deletion of the TEK receptor results in failure of SC development and rapidly progressing ocular hypertension (7,8). However, while the importance of ANGPT/TEK signaling in canal development and associated aqueous humor drainage is clear, the individual roles for each of the major ANGPT ligands are not understood.…”

Section: Angpt1 and Angpt2 Are Expressed In The Iridocorneal Anglementioning

confidence: 99%

“…Despite the central role of SC in IOP maintenance and disease, no pharmacological tools targeting the canal are currently available in the clinic. Recently, however, the importance of endothelial growth factor signaling has been appreciated, and critical roles for both the VEGF/VEGFR and the ANGPT/TEK pathway have been described (5)(6)(7)(8), identifying an array of potential targets for future therapeutic development.…”

Section: Introductionmentioning

confidence: 99%

“…Angiopoietin-1 is required for Schlemm's canal development in mice and humans Benjamin R. Thomson Liang Feng, 6 Kristina N. Whisenhunt, 3 Tammy L. Yanovitch, 7 Luba Kalaydjieva, 8 Dimitar N. Azmanov, 8,9 Simone Finzi, 10 Christine E. Tanna, 1,2 Alex W. Hewitt, 11,12,13 David A. Mackey, 12,13 Yasmin S. Bradfield, 3 Emmanuelle Souzeau, 5 Shari Javadiyan, 5 Janey L. Wiggs, 14 Francesca Pasutto, 15 Xiaorong Liu, 6 Simon W.M. John, 4 Jamie E. Craig, 5 Jing Jin, 1,2 Terri L. Young, 3 and Susan E. Quaggin…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Thomson

Souma²,

Tompson

et al. 2017

Journal of Clinical Investigation

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118

113

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Section: Discussionmentioning

confidence: 71%

Section: Angpt1 and Angpt2 Are Expressed In The Iridocorneal Anglementioning

confidence: 99%

Section: Angpt1 and Angpt2 Are Expressed In The Iridocorneal Anglementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Thomson

Souma²,

Tompson

et al. 2017

Journal of Clinical Investigation

Self Cite

118

113

View full text Add to dashboard Cite

Prevalence ofFOXC1Variants in Individuals With a Suspected Diagnosis of Primary Congenital Glaucoma

et al. 2019

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IMPORTANCE Both primary and secondary forms of childhood glaucoma have many distinct causative mechanisms, and in many cases a cause is not immediately clear. The broad phenotypic spectrum of secondary glaucoma, particularly in individuals with variants in FOXC1 or PITX2 genes associated with Axenfeld-Rieger syndrome, makes it more difficult to diagnose patients with milder phenotypes. These cases are occasionally classified and managed as primary congenital glaucoma. OBJECTIVE To investigate the prevalence of FOXC1 variants in participants with a suspected diagnosis of primary congenital glaucoma.

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Consistent Intraocular Pressure Reduction by Solid Drug Nanoparticles in Fixed Combinations for Glaucoma Therapy

Huang,

Norat,

et al. 2024

Advanced Science

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Efficient topical drug delivery remains a significant challenge in glaucoma management. Although nanoparticle formulations offer considerable promise, their complex preparation processes, co‐delivery issues, and batch consistency have hindered their potential. A scalable fabrication strategy is developed here for preparing solid drug nanoparticles (SDNs) with enhanced drug delivery efficiency. Utilizing hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX), uniform fixed combination BM/BX SDNs are fabricated through a continuous process, improving batch‐to‐batch consistency for combined glaucoma treatment. With trehalose being used as a lyoprotectant, BM/BX SDNs can be stored as dry powder and easily reconstituted in phosphate buffered saline. Importantly, reconstituted BM/BX SDNs form clear, homogenous solutions, and exhibit negligible cytotoxicity and irritation, making them well‐suited for topical administration as eyedrops. Ex vivo and in vivo studies demonstrated that topically applied BM/BX SDNs permeate through the cornea significantly (about two fold to three fold) compared to their hydrophilic counterparts, i.e., brimonidine tartrate, and betaxolol hydrogen chloride. Notably, BM/BX SDNs displayed consistent intraocular pressure lowering effects in vivo in both normotensive rats and glaucoma mice. Collectively, this study demonstrates the potential of the scalable fabrication strategy and the resultant BM/BX SDNs for improving glaucoma management through eyedrops.

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Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

Cited by 203 publications

References 63 publications

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Angiopoietin-1 is required for Schlemm’s canal development in mice and humans

Prevalence ofFOXC1Variants in Individuals With a Suspected Diagnosis of Primary Congenital Glaucoma

Consistent Intraocular Pressure Reduction by Solid Drug Nanoparticles in Fixed Combinations for Glaucoma Therapy

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