Matthew Benson
University of Alberta, Ophthalmology & Visual Sciences, Department Member
Stargardt-like macular dystrophy (STGD3) represents an early onset, autosomal dominant form of macular degeneration. Genetic studies revealed that STGD3 is caused by mutations in the ELOngation of Very Long chain fatty acids-4 ( ELOVL4 )... more
Stargardt-like macular dystrophy (STGD3) represents an early onset, autosomal dominant form of macular degeneration. Genetic studies revealed that STGD3 is caused by mutations in the ELOngation of Very Long chain fatty acids-4 ( ELOVL4 ) gene on the short arm of human chromosome 6 (1). As its name implies, STGD3 has a clinical profile that is very similar to Stargardt macular degeneration (STGD1), which is characterized by progressive central vision loss, macular atrophy, RPE degeneration, and presence of yellow flecks. We present a case of an STGD3 patient with typical retinal features and an unu-sual keratopathy.
Research Interests:
Stargardt-like macular dystrophy (STGD3) represents an early onset, autosomal dominant form of macular degeneration. Genetic studies revealed that STGD3 is caused by mutations in the ELOngation of Very Long chain fatty acids-4 ( ELOVL4 )... more
Stargardt-like macular dystrophy (STGD3) represents an early onset, autosomal dominant form of macular degeneration. Genetic studies revealed that STGD3 is caused by mutations in the ELOngation of Very Long chain fatty acids-4 ( ELOVL4 ) gene on the short arm of human chromosome 6 (1). As its name implies, STGD3 has a clinical profile that is very similar to Stargardt macular degeneration (STGD1), which is characterized by progressive central vision loss, macular atrophy, RPE degeneration, and presence of yellow flecks. We present a case of an STGD3 patient with typical retinal features and an unu-sual keratopathy.
Research Interests:
Research Interests:
Research Interests:
To report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association. We describe a 35-week-old girl with previously... more
To report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association. We describe a 35-week-old girl with previously diagnosed CHARGE syndrome who presented with corneal edema, buphthalmos, and elevated intraocular pressure in the left eye. She was subsequently diagnosed with congenital glaucoma and started on topical and oral therapy. Examination under anesthesia confirmed the above findings as well as bilateral abnormal angles with an anterior iris insertion at the level of the posterior trabecular meshwork, prominent iris vasculature and stromal strands, and nonvisible scleral spur and ciliary body bands. Trabeculotomy and trabeculectomy were performed in the left eye with a poor outcome. CHARGE syndrome is a complex neurocristopathy, and we propose that the abnormal angle findings and associated asymmetric glaucoma in our patient share a common mechanism of neural crest cell dysfunction. CHARGE syndrome can be associated with congenital glaucoma and we emphasize the importance of a thorough ophthalmic examination to detect glaucoma with surgical management as deemed appropriate.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Biology, Membrane Proteins, Cell Biology, Mitochondria, Medicine, and 15 moreBiological Sciences, Dogs, Humans, Mice, Melanoma, Animals, Endoplasmic Reticulum, Heme Oxygenase, HeLa cells, Cysteine, Amino Acid Sequence, Membrane Protein, Molecular Sequence Data, Lipoylation, and Medical and Health Sciences
The palmitoylation of calnexin serves to enrich calnexin on the mitochondria-associated membrane (MAM). Given a lack of information on the significance of this finding, we have investigated how this endoplasmic reticulum (ER)-internal... more
The palmitoylation of calnexin serves to enrich calnexin on the mitochondria-associated membrane (MAM). Given a lack of information on the significance of this finding, we have investigated how this endoplasmic reticulum (ER)-internal sorting signal affects the functions of calnexin. Our results demonstrate that palmitoylated calnexin interacts with sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA) 2b and that this interaction determines ER calcium content and the regulation of ER-mitochondria calcium crosstalk. In contrast, non-palmitoylated calnexin interacts with the oxidoreductase ERp57 and performs its well-known function in quality control. Interestingly, our results also show that calnexin palmitoylation is an ER stress-dependent mechanism. Following a short term ER stress, calnexin quickly becomes less palmitoylated, which shifts its function from the regulation of calcium signaling towards chaperoning and quality control of known substrates. These changes als...
Research Interests: Biology, Calcium, Cell Biology, Mitochondria, Endoplasmic Reticulum Stress, and 15 moreMedicine, Biological Sciences, Cell line, Humans, Mice, Animals, Endoplasmic Reticulum, Calcium Signaling, T cells, HeLa cells, Palmitoylation, calreticulin, fibroblasts, Lipoylation, and Medical and Health Sciences
The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role... more
The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role in the onset of ER stress-mediated apoptosis, likely through the modulation of ER calcium signaling. These opposing roles of MAM-localized chaperones suggest the existence of mechanisms that regulate the composition and the properties of ER membrane domains. Our results now show that the GTPase Rab32 localizes to the ER and mitochondria, and we identify this protein as a regulator of MAM properties. Consistent with such a role, Rab32 modulates ER calcium handling and disrupts the specific enrichment of calnexin on the MAM, while not affecting the ER distribution of protein-disulfide isomerase and mitofusin-2. Furthermore, Rab32 determines the targeting of PKA to mitochondrial and ER membranes and through its overexpression or inactivation increases...
Research Interests: Biology, Calcium, Membrane Proteins, Cell Biology, Mitochondria, and 15 moreBiological Chemistry, Apoptosis, Medicine, Biological Sciences, Molecular chaperones, Humans, Biological, Unfolded Protein Response, Endoplasmic Reticulum, CHEMICAL SCIENCES, HeLa cells, Regulator, Mitochondrion, Mitochondrial Proteins, and Medical and Health Sciences
Research Interests: Biology and Peroxisome
Research Interests: Genetics, Dermatology, Medicine, Visual acuity, Humans, and 4 moreFemale, Uveitis, Middle Aged, and Medical Case Reports
Research Interests:
Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of... more
Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3. Whole exome sequencing and Sanger sequencing of patients with coloboma identified three variants in BMP3, two of which are predicted to be disease causing. Consistent with this, bmp3 mutant zebrafish have aberrant fissure closure. bmp3 is expressed in the ventral head mesenchyme and regulates phosphorylated Smad3 in a population of cells adjacent to the choroid fissure. Furthermore, mutations in bmp3 sensitize embryos to Smad3 inhibitor treatment resulting in open choroid fissures. Micro CT scans and Alcian blue staining of zebrafish demonstrate that mutations in bmp3 cause midface hypoplasia, suggesting that bmp3 regulates cranial neural crest cells....
To evaluate the ability of a targeted genome-wide association study (GWAS) to identify genes associated with central corneal thickness (CCT). A targeted GWAS was used to investigate whether ten candidate genes with known roles in corneal... more
To evaluate the ability of a targeted genome-wide association study (GWAS) to identify genes associated with central corneal thickness (CCT). A targeted GWAS was used to investigate whether ten candidate genes with known roles in corneal development were associated with CCT in two Singaporean populations. The single nucleotide polymorphisms (SNPs) within a 500 kb interval encompassing each candidate were analyzed, and in light of the resulting data, members of the Wnt pathway were subsequently screened using similar methodology. Variants within the 500 kb interval encompassing three candidate genes, (rs1896368, p=1.32×10), (rs17510449, p=7.34×10), and (rs7326616, p=1.56×10 and rs4943785, p=1.19×10), were statistically significantly associated with CCT in the Singapore Indian population. was statistically significantly associated with CCT in a separate Singapore Malaysian population (rs10015200, p=2.26×10). Analysis of Wnt signaling pathway genes in each population demonstrated that ...
Research Interests:
To describe a case of Stevens-Johnson syndrome (SJS) diagnosed in a patient presenting with primarily ocular findings where SJS had not been initially suspected. A 23-year-old female presented with a 2 day history of bilateral eye pain,... more
To describe a case of Stevens-Johnson syndrome (SJS) diagnosed in a patient presenting with primarily ocular findings where SJS had not been initially suspected. A 23-year-old female presented with a 2 day history of bilateral eye pain, conjunctival injection, decreased visual acuity, and photophobia in the context of a 4 day history of fever, headache, and sore throat. She was found to have bilateral superficial keratitis and treated for suspected early infectious keratitis secondary to extended contact lens wear. She returned the next day with worsening visual symptoms, a new macular rash over her upper torso, and new ulcerating lesions over her buccal and perioral tissue. The patient was diagnosed with SJS. She was successfully treated using systemic cyclosporine with antibiotics and steroid eye drops. Ophthalmologists may be the first physicians to diagnose SJS, a life-threatening condition that can initially present with non-specific viral prodromal symptoms and ocular signs al...
Research Interests:
Dilated cardiomyopathy with ataxia syndrome (DCMA) is a rare mitochondrial condition associated with early onset cardiomyopathy and non-progressive ataxia. The cardiac manifestations may be progressive and often severe, resulting in... more
Dilated cardiomyopathy with ataxia syndrome (DCMA) is a rare mitochondrial condition associated with early onset cardiomyopathy and non-progressive ataxia. The cardiac manifestations may be progressive and often severe, resulting in significant morbidity and mortality. While optic nerve atrophy has been described in patients with DCMA, to our knowledge, there have been no reports of additional ocular phenotypes. We present two related Dariusleut Hutterite patients with documented DCMA syndrome and disorders of ocular motility: poor smooth pursuit and difficulty initiating saccadic eye movements and maintaining target fixation. We thus report the first cases of oculomotor apraxia in DCMA syndrome. By identifying these associated findings early in life, we hope to improve both the clinical diagnostic accuracy and timeliness of intervention in cases of DCMA.
Research Interests:
Research Interests:
Research Interests:
Introduction: Usher syndrome is a genetically heterogeneous condition and represents the most common cause of inherited combined vision and hearing loss. Deficits manifest as sensorineural hearing loss that typically develops at a young... more
Introduction: Usher syndrome is a genetically heterogeneous condition and represents the most common cause of inherited combined vision and hearing loss. Deficits manifest as sensorineural hearing loss that typically develops at a young age and retinitis pigmentosa that can lead to peripheral vision loss and night blindness. As a result, this syndrome can have a significant impact on a patient's quality of life. Previous studies have described an association between Usher syndrome and Fuchs' heterochromic iridocyclitis, a form of non-granulomatous uveitis that generally presents in a unilateral manner. We present a rare finding of bilateral uveitis and, to the best of our knowledge, the first report of granulomatous uveitis as a feature in a patient with Usher syndrome. Case presentation: A 45-year-old Caucasian woman with a known history of retinitis pigmentosa presented to our clinic with suspected Usher syndrome, given her report of long-standing hearing loss. Aside from a mild loss in visual acuity, our patient was otherwise asymptomatic. Visual field testing, audiology and electroretinography findings supported the diagnosis of Usher syndrome. With slit lamp examination she was found to have bilateral keratic precipitates, with large, greasy-white, mutton-fat keratic precipitates on the endothelial surface of her left eye. A thorough work-up that included blood tests and imaging was negative for an alternative cause of her uveitis. Conclusion: We present a rare finding of bilateral uveitis and what we believe to be the first reported instance of mutton-fat keratic precipitates and granulomatous uveitis as a feature in a patient with Usher syndrome. By identifying atypical presentations of the disease, we hope to contribute to the range of ophthalmic conditions that may be seen in association with Usher syndrome.
Research Interests:
Purpose: To report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association. Patients and Methods: We describe a... more
Purpose: To report a rare case of congenital glaucoma in a patient with CHARGE syndrome, present gonioscopic photographs, and explore mechanisms of disease that may account for this association. Patients and Methods: We describe a 35-week-old girl with previously diagnosed CHARGE syndrome who presented with cor-neal edema, buphthalmos, and elevated intraocular pressure in the left eye. She was subsequently diagnosed with congenital glaucoma and started on topical and oral therapy. Results: Examination under anesthesia confirmed the above findings as well as bilateral abnormal angles with an anterior iris insertion at the level of the posterior trabecular meshwork, prominent iris vasculature and stromal strands, and nonvisible scleral spur and ciliary body bands. Trabeculotomy and trabeculectomy were performed in the left eye with a poor outcome. CHARGE syndrome is a complex neurocristopathy, and we propose that the abnormal angle findings and associated asymmetric glaucoma in our patient share a common mechanism of neural crest cell dysfunction. Conclusions: CHARGE syndrome can be associated with congenital glaucoma and we emphasize the importance of a thorough ophthalmic examination to detect glaucoma with surgical management as deemed appropriate. C HARGE syndrome is a rare genetic condition associated with numerous systemic manifestations. Clinically , CHARGE syndrome includes coloboma, heart defects, choanal atresia, retardation of growth and development , genito-urinary malformations, and ear abnormalities. Although several ocular phenotypes such as coloboma have been described frequently in association with CHARGE syndrome, congenital glaucoma, to the best of our knowledge, has only been described twice in these patients. We report a 35-week-old girl with corneal edema and enlargement, elevated intraocular pressure (IOP) and buphthalmos leading to a diagnosis of congenital glaucoma in addition to bilateral asymmetric optic nerve colobomas. In addition, our patient demonstrated abnormal angle features that differ from those seen in isolated primary congenital glaucoma. We thus report only the third case of congenital glaucoma in CHARGE syndrome and present the first gonioscopic photographs in these patients. We hypothesize that aberrant neural crest cell function underlies the association between CHARGE syndrome and developmental glaucoma in our patient. By contributing to the knowledge of mechanisms of disease in patients with CHARGE syndrome and congenital glaucoma, we hope that early diagnosis and intervention can be offered to prevent irreversible vision loss in these patients. CASE REPORT A 35-week-old white female with CHARGE syndrome presented for ophthalmic assessment after her parents had identified left corneal clouding, apparent globe enlargement, and tearing from the left eye. Her medical history included a full-term birth following an uneventful pregnancy. Her parents were non-consanguineous and there was no family history of CHARGE syndrome or congenital glaucoma. CHARGE syndrome had initially been suspected when, shortly after delivery, she had been found to have bilateral choanal atresia that required endoscopic repair. An echocardiogram ordered after she had experienced episodes of supraventricular tachycardia had revealed 2 atrial septal defects. Evaluation at that time had revealed the presence of bilateral optic nerve colobomas. Imaging of the temporal bones and internal auditory canals had revealed bilateral dysplastic cochleae and semicircular canals resulting in bilateral sensorineural hearing loss. Array comparative genomic hybridization had been normal. Taken together, the clinical findings in this patient had met FIGURE 1. Anterior segment examination with retroillumination of the left eye in a patient with CHARGE syndrome. An enlarged corneal diameter is evident along with extensive Haab's striae. Figure 1 can viewed in color online at
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role... more
The mitochondria-associated membrane (MAM) has emerged as an endoplasmic reticulum (ER) signaling hub that accommodates ER chaperones, including the lectin calnexin. At the MAM, these chaperones control ER homeostasis but also play a role in the onset of ER stress-mediated apoptosis, likely through the modulation of ER calcium signaling. These opposing roles of MAM-localized chaperones suggest the existence of mechanisms that regulate the composition and the properties of ER membrane domains. Our results now show that the GTPase Rab32 localizes to the ER and mitochondria, and we identify this protein as a regulator of MAM properties. Consistent with such a role, Rab32 modulates ER calcium handling and disrupts the specific enrichment of calnexin on the MAM, while not affecting the ER distribution of protein-disulfide isomerase and mitofusin-2. Furthermore, Rab32 determines the targeting of PKA to mitochondrial and ER membranes and through its overexpression or inactivation increases...