Ptr1 and ZAR1 immune receptors confer overlapping and distinct bacterial pathogen effector specificities.

Some nucleotide-binding and leucine-rich repeat receptors (NLRs) indirectly detect pathogen effectors by monitoring their host targets. In Arabidopsis thaliana, RIN4 is targeted by multiple sequence-unrelated effectors and activates immune responses mediated by RPM1 and RPS2. These effectors trigger cell death in Nicotiana benthamiana, but the corresponding NLRs have yet not been identified. To identify N. benthamiana NLRs (NbNLRs) that recognize Arabidopsis RIN4-targeting effectors, we conducted a rapid reverse genetic screen using an NbNLR VIGS library. We identified that the N. benthamiana homolog of Ptr1 (Pseudomonas tomato race 1) recognizes the Pseudomonas effectors AvrRpt2, AvrRpm1, and AvrB. We demonstrated that recognition of the Xanthomonas effector AvrBsT and the Pseudomonas effector HopZ5 is conferred independently by the N. benthamiana homolog of Ptr1 and ZAR1. Interestingly, the recognition of HopZ5 and AvrBsT is contributed unequally by Ptr1 and ZAR1 in N. benthamiana and Capsicum annuum. In addition, we showed that the RLCK XII family protein JIM2 is required for the NbZAR1-dependent recognition of AvrBsT and HopZ5. The recognition of sequence-unrelated effectors by NbPtr1 and NbZAR1 provides an additional example of convergently evolved effector recognition. Identification of key components involved in Ptr1 and ZAR1-mediated immunity could reveal unique mechanisms of expanded effector recognition.

The Ralstonia pseudosolanacearum effector RipE1 is recognized at the plasma membrane by NbPtr1, the Nicotiana benthamiana homologue of Pseudomonas tomato race 1.

The bacterial wilt disease caused by soilborne bacteria of the Ralstonia solanacearum species complex (RSSC) threatens important crops worldwide. Only a few immune receptors conferring resistance to this devastating disease are known so far. Individual RSSC strains deliver around 70 different type III secretion system effectors into host cells to manipulate the plant physiology. RipE1 is an effector conserved across the RSSC and triggers immune responses in the model solanaceous plant Nicotiana benthamiana. Here, we used multiplexed virus-induced gene silencing of the nucleotide-binding and leucine-rich repeat receptor family to identify the genetic basis of RipE1 recognition. Specific silencing of the N. benthamiana homologue of Solanum lycopersicoides Ptr1 (confers resistance to Pseudomonas syringae pv. tomato race 1) gene (NbPtr1) completely abolished RipE1-induced hypersensitive response and immunity to Ralstonia pseudosolanacearum. The expression of the native NbPtr1 coding sequence was sufficient to restore RipE1 recognition in Nb-ptr1 knockout plants. Interestingly, RipE1 association with the host cell plasma membrane was necessary for NbPtr1-dependent recognition. Furthermore, NbPtr1-dependent recognition of RipE1 natural variants is polymorphic, providing additional evidence for the indirect mode of activation of NbPtr1. Altogether, this work supports NbPtr1 relevance for resistance to bacterial wilt disease in Solanaceae.

Two plant NLR proteins confer strain-specific resistance conditioned by an effector from Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker, a devastating disease threatening the Actinidia fruit industry. In a search for non-host resistance genes against Psa, we find that the nucleotide-binding leucine-rich repeat receptor (NLR) protein ZAR1 from both Arabidopsis and Nicotiana benthamiana (Nb) recognizes HopZ5 and triggers cell death. The recognition requires ZED1 in Arabidopsis and JIM2 in Nb plants, which are members of the ZRK pseudokinases and known components of the ZAR1 resistosome. Surprisingly, Arabidopsis ZAR1 and RPM1, another NLR known to recognize HopZ5, confer disease resistance to HopZ5 in a strain-specific manner. Thus, ZAR1, but not RPM1, is solely required for resistance to P. s. maculicola ES4326 (Psm) carrying hopZ5, whereas RPM1 is primarily required for resistance to P. s. tomato DC3000 (Pst) carrying hopZ5. Furthermore, the ZAR1-mediated resistance to Psm hopZ5 in Arabidopsis is insensitive to SOBER1, which encodes a deacetylase known to suppress the RPM1-mediated resistance to Pst hopZ5. In addition, hopZ5 enhances P. syringae virulence in the absence of ZAR1 or RPM1 and that SOBER1 abolishes such virulence function. Together the study suggests that ZAR1 may be used for improving Psa resistance in Actinidia and uncovers previously unknown complexity of effector-triggered immunity and effector-triggered virulence.

Assessment for Macular Thickness after Uncomplicated Phacoemulsification Using Optical Coherence Tomography.

PURPOSE: Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study. METHODS: Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT. RESULTS: A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range. CONCLUSIONS: The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.

Morphological change of the posterior pole following the horizontal strabismus surgery with swept source optical coherence tomography.

Extraocular muscle movement during strabismus surgery causes changes in eyeball shape. Because extraocular muscle insertion is in front of the equator, it is thought that changes due to strabismus surgery mainly occur in the anterior segment. However, changes in the posterior segment of eye may also occur, which may also result in changes in refractive error after strabismus surgery. Using a 3-dimensional reconstruction technique (en face imaging) of the swept source optical coherence tomography, we determined and quantitatively measured the posterior polar change. The deepest interface between Bruch's membrane and the choroid could be identified as the deepest point of the eyeball (DPE), and the location of the DPE relative to the optic disc and the fovea was measured. After lateral rectus muscle recession, the DPE moved away from the fovea, but after medial rectus muscle recession, the DPE moved toward the fovea. The amount of DPE movement differed by age and preoperative refractive error. Our findings suggest that the positional shift of the rectus muscle in horizontal strabismus surgery causes a structural change in the posterior segment of the eye, and the postoperative refractive changes may be related to this shift.

Compressive Optic Neuropathy with a Concurrent Mutation of Leber's Hereditary Optic Neuropathy: A Case Report.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that leads to acute or subacute, painless, bilateral loss of vision, caused by degeneration of retinal ganglion cells that most affects men in their second or third decade of life. We describe a woman with compressive optic neuropathy with a concurrent LHON-associated mitochondrial mutation. Temporal hemifield defect connected to central scotoma and concurrent abduction limitation are diagnostic clues in identifying chiasmal compression with craniopharyngioma. This case emphasizes an awareness of the possible coexistence of compressive and hereditary optic neuropathy.

Interocular difference associated with myopic progression following unilateral lateral rectus recession in early school-aged children.

PURPOSE: To compare refractive changes in operated eyes and fellow unoperated eyes following unilateral lateral rectus recession in early school-aged children. STUDY DESIGN: A retrospective case control study. METHODS: The medical records of children under ten years of age with intermittent exotropia who underwent unilateral lateral recession surgery were reviewed. The operated eyes were reviewed and the fellow unoperated eyes were used as control. The rate of myopic progression was calculated by spherical equivalent (SE) changes per year, and by the rate of refractive growth (RRG) equation. RESULTS: SE showed a myopic shift one week after surgery and in the following months, from -1.43 ± 1.84 diopters (D) at 1 week post operation to -1.57 ± 2.22 D at one year and, finally -2.95 ± 2.97 D at the average 4.62 years following surgery. However, the SE shift was not significantly different from the unoperated eye. The low myopia group (under -3.0 D) showed a significantly higher myopic change in the operated eye until one year post operation (p = 0.022). The average myopic shift ratio was -0.53 ± 0.46 D yearly in the operated eye. CONCLUSIONS: This study presents data of a large series of refractive changes secondary to lateral rectus recession, and of long-term myopia progression in Korean population.

Surgical and sensory outcomes in patients with intermittent exotropia according to preoperative refractive error.

BACKGROUND/OBJECTIVES: To analyze the surgical and sensory outcomes of intermittent exotropia according to refractive errors and the factors associated with surgical success. SUBJECTS/METHODS: A total of 326 children were divided into three groups according to preoperative refractive error; hyperopic eyes with SE ≥+2D (hyperopic group), eyes with SE between -1D and +2D (emmetropic group), and myopic eyes with SE ≤-1D (myopic group). The surgical outcomes and the sensory outcomes measured by near and distant stereoacuity were compared among the three groups. RESULTS: The surgical success rate in hyperopic group was significantly lower compared to myopic group at last follow-up (P = 0.012). Preoperative near stereopsis was not different among three groups, however, the distance stereopsis was significantly deteriorated in the hyperopic group compared to the other two groups (Titmus; P = 0.168, FD2; P < 0.001, DR; P = 0.048). There was postoperative improvement in both near and distant stereopsis in all three groups (Titmus; P = 0.009, FD2; P = 0.021, DR; P = 0.036) and no significant difference was found in the postoperative distant stereopsis among the three groups. CONCLUSIONS: Preoperative refractive error is a prognostic factor of surgical success in patients with intermittent exotropia. Patients with hyperopia achieved less favorable surgical outcome compared to myopic patients. The preoperative distant stereoacuity was decreased in hyperopic patients compared to myopic patients, which eventually improved after surgery and showed no significant difference at postoperative measurements.

Clinical features of posterior microphthalmos associated with papillomacular fold and high hyperopia.

BACKGROUND: The aim was to evaluate the characteristic clinical features of posterior microphthalmos. METHODS: Medical records of four patients (eight eyes) between the ages of three and 31 years with posterior microphthalmos were reviewed retrospectively. Thorough ocular examinations were performed, including visual acuity, intraocular pressure, ocular alignment, axial length, cycloplegic refraction, slitlamp biomicroscopy of the anterior segment and fundus and spectral-domain optical coherent tomography (SD-OCT). RESULTS: All subjects had presented with high hyperopia (+11.0 to +15.75 D) and retinal papillomacular folds in both eyes. They also had reduced bilateral axial length (15.55-18.61 mm), with foreshortening of the posterior segment and a relatively normal anterior segment. Papillomacular retinal folds involving the inner retinal layers and sparing the outer retinal layers, along with the absence of foveal depression, were confirmed by macular SD-OCT. In three patients, we found esodeviations associated with posterior microphthalmos and one of these required strabismic surgery. Concomitant optic nerve hypoplasia and a newly-developed neurosensory retinal detachment were found in one patient. CONCLUSION: Posterior microphthalmos is a developmental arrest of ocular growth. In addition to high hyperopia and retinal papillomacular folds, various types of esotropia, optic disc hypoplasia and neurosensory retinal detachment may accompany posterior microphthalmos. In particular, children with posterior microphthalmos require early appropriate management of the high refractive error and resultant esotropia.

Calpain and Caspase-12 Expression in Lens Epithelial Cells of Diabetic Cataracts.

PURPOSE: To compare the expression of calpain and caspase-12 in human lens epithelial cells (LECs) of cataract patients with or without diabetic retinopathy (DR). DESIGN: Prospective, comparative case series. METHODS: Patients were divided into 4 groups: patients without diabetes mellitus (DM) (Group 1), patients with DM and without diabetic retinopathy (DR) (Group 2), diabetic patients with nonprolifeative DR (NPDR) (Group 3), and diabetic patients with proliferative DR (PDR) (Group 4). Data on DM duration and glycated hemoglobin (HbA1c) level were collected. The LECs were obtained during cataract surgery and immunohistochemical staining was performed for calpain and caspase-12. The reactivity score of each specimen was determined using confocal microscopy. RESULTS: A total of 40 patients (40 eyes) were evaluated, and each group was composed of 10 patients. The expression of calpain and caspase-12 was highest in Group 4, followed by Group 3, Group 2, and Group 1 (P < .001). The expressions were significantly higher with a longer duration of DM, increased HbA1c level, or advanced DR. CONCLUSIONS: Endoplasmic reticulum stress may be associated with apoptosis of LECs, resulting in cataract formation in diabetic patients.

Comparison of macular thickness and inflammatory cytokine levels after microincision versus small incision coaxial cataract surgery.

PURPOSE: To compare the macular thickness and volume change, and inflammatory cytokine levels after cataract surgery performed using two different sizes of incision (microincision versus small incision). METHODS: In this randomized, comparative clinical trial, 84 eyes with nuclear density from Grade 3-4 were randomly divided into two groups (microincision, 2.2 mm; and small incision, 2.75 mm). Forty-two patients underwent phacoemulsification with microincision coaxial cataract surgery and 42 patients underwent phacoemulsification with small incision coaxial cataract surgery. Clinical measurements included preoperative, 1-week, 1-month and 2-month postoperative best corrected visual acuity, central corneal thickness (CCT) and endothelial cell count. ELISA and RT-PCR were performed for IL-1ß, IL-6, VEGF and PGE2 preoperatively and at 1 week postoperatively. RESULTS: The percentage increase in CCT in the microincision group was significantly higher than that in the small incision group at 1 week after cataract surgery (p = 0.01). The increase in macular thickness in the microincision group was significantly higher than that in small incision group at 1 month after cataract operation (p = 0.04). Also, IL-1ß, IL-6, VEGF and PGE2 concentrations and their expression ratio in the microincision group were significantly higher than those in the small incision group at 1 week after cataract surgery compared to the preoperative period (p < 0.05). CONCLUSIONS: Phacoemulsification with microincision coaxial cataract surgery may increase the macular thickness compared to phacoemulsification with small incision coaxial cataract surgery. Blood-aqueous barrier breakdown may occur more frequently after microincision cataract surgery than after small incision cataract surgery.

Risk factors of persistent diplopia following secondary intraocular lens implantation in patients with sensory strabismus from uncorrected monocular aphakia.

PURPOSE: We aimed to compare clinical characteristics between diplopia-free and diplopia-persistent patients after successful strabismus surgery, when patients complained of diplopia following secondary intraocular lens (IOL) implantation after prolonged aphakia accompanied by sensory strabismus. METHODS: Retrospective review of medical records of patients who complained of diplopia following secondary IOL placement with sensory strabismus after prolonged uncorrected monocular aphakia from isolated ocular trauma was done. We classified patients into two groups according to persistency of diplopia, 6 months after successful strabismus surgery. Clinical characteristics were compared between groups. RESULTS: A total of 31 patients were included. The diplopia-persistent group showed longer duration of uncorrected aphakia (p = 0.02), less severe corneal astigmatism (p = 0.04), a smaller exodeviation angle (p = 0.02), and more frequent vertical deviation (p = 0.015), extorsion (p = 0.022) and monocular nystagmus (p = 0.028) than the diplopia-free group. In all patients in the diplopia-free group, diplopia could be eliminated prior to strabismus surgery using loose prisms in free space, whereas seven patients in the diplopia-persistent group prior to surgery could not resolve diplopia. CONCLUSIONS: Our data will be helpful for ocular surgeons in determining whether to insert secondary IOL in prolonged aphakia with sensory strabismus, or whether strabismus surgery will eliminate diplopia that develops following secondary IOL placement in this situation.

Ranibizumab injection for corneal neovascularization refractory to bevacizumab treatment.

Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.

Lacrimal gland fistula after cosmetic lateral canthoplasty.

BACKGROUND: We report a case of lacrimal gland fistula formation after cosmetic lateral canthoplasty in a young Asian woman. PATIENT: A 34-year-old woman, who twice underwent lateral canthoplasties of both eyes with additional upper eyelid blepharoplasty, developed clear fluid discharge from a small draining tract near the lateral canthus after being operated on with cosmetic lateral canthoplasty. Assuming that lacrimal gland fistula has developed, we differentiated the tract from the lacrimal gland using a Bowman probe and performed lacrimal gland fistulectomy, which resolved the discharge, leaving no complications. CONCLUSIONS: To our knowledge, this is the first case of lacrimal gland fistula after cosmetic lateral canthoplasty, and surgeons performing this procedure should be aware of lacrimal gland herniation and fistula tract formation, especially in patients who have undergone multiple eyelid surgeries.