Chemical bond reorganization in intramolecular proton transfer revealed by ultrafast X-ray photoelectron spectroscopy.

Time-resolved X-ray photoelectron spectroscopy (TR-XPS) is used in a simulation study to monitor the excited state intramolecular proton transfer between oxygen and nitrogen atoms in 2-(iminomethyl)phenol. Real-time monitoring of the chemical bond breaking and forming processes is obtained through the time evolution of excited-state chemical shifts. By employing individual atomic probes of the proton donor and acceptor atoms, we predict distinct signals with opposite chemical shifts of the donor and acceptor groups during proton transfer. Details of the ultrafast bond breaking and forming dynamics are revealed by extending the classical electron spectroscopy chemical analysis to real time. Through a comparison with simulated time-resolved photoelectron spectroscopy at the valence level, the distinct advantage of TR-XPS is demonstrated thanks to its atom specificity.

Cavity Control of Molecular Spectroscopy and Photophysics.

ConspectusOptical cavities have been established as a powerful platform for manipulating the spectroscopy and photophysics of molecules. Molecules placed inside an optical cavity will interact with the cavity field, even if the cavity is in the vacuum state with no photons. When the coupling strength between matter excitations, either electronic or vibrational, and a cavity photon mode surpasses all decay rates in the system, hybrid light-matter excitations known as cavity polaritons emerge. Originally studied in atomic systems, there has been growing interest in studying polaritons in molecules. Numerous studies, both experimental and theoretical, have demonstrated that the formation of molecular polaritons can significantly alter the optical, electronic, and chemical properties of molecules in a noninvasive manner.This Account focuses on novel studies that reveal how optical cavities can be employed to control electronic excitations, both valence and core, in molecules and the spectroscopic signatures of molecular polaritons. We first discuss the capacity of optical cavities to manipulate and control the intrinsic conical intersection dynamics in polyatomic molecules. Since conical intersections are responsible for a wide range of photochemical and photophysical processes such as internal conversion, photoisomerization, and singlet fission, this provides a practical strategy to control molecular photodynamics. Two examples are given for the internal conversion in pyrazine and singlet fission in a pentacene dimer. We further show how X-ray cavities can be exploited to control the core-level excitations of molecules. Core polaritons can be created from inequivalent core orbitals by exchanging X-ray cavity photons. The core polaritons can also alter the selection rules in nonlinear spectroscopy.Polaritonic states and dynamics can be monitored by nonlinear spectroscopy. Quantum light spectroscopy is a frontier in nonlinear spectroscopy that exploits the quantum-mechanical properties of light, such as entanglement and squeezing, to extract matter information inaccessible by classical light. We discuss how quantum spectroscopic techniques can be employed for probing polaritonic systems. In multimolecule polaritonic systems, there exist two-polariton states that are dark in the two-photon absorption spectrum due to destructive interference between transition pathways. We show that a time-frequency entangled photon pair can manipulate the interference between transition pathways in the two-photon absorption signal and thus capture classically dark two-polariton states. Finally, we discuss cooperative effects among molecules in spectroscopy and possibly in chemistry. When many molecules are involved in forming the polaritons, while the cooperative effects clearly manifest in the dependence of the Rabi splitting on the number of molecules, whether they can show up in chemical reactivity, which is intrinsically local, is an open question. We explore the cooperative nature of the charge migration process in a cavity and show that, unlike spectroscopy, polaritonic charge dynamics is intrinsically local and does not show collective many-molecule effects.

Manipulating Attosecond Charge Migration in Molecules by Optical Cavities.

The ultrafast electronic charge dynamics in molecules upon photoionization while the nuclear motions are frozen is known as charge migration. In a theoretical study of the quantum dynamics of photoionized 5-bromo-1-pentene, we show that the charge migration process can be induced and enhanced by placing the molecule in an optical cavity, and can be monitored by time-resolved photoelectron spectroscopy. The collective nature of the polaritonic charge migration process is investigated. We find that, unlike spectroscopy, molecular charge dynamics in a cavity is local and does not show many-molecule collective effects. The same conclusion applies to cavity polaritonic chemistry.

Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation.

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I-120 /I+40 ), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.

Extended Koopmans' theorem at the second-order perturbation theory.

The extended Koopmans' theorem (EKT), when combined with the second-order Møller-Plesset (MP2) perturbation theory through the relaxed density matrix approach [J. Cioslowski, P. Piskorz, and G. Liu, J. Chem. Phys. 1997, 107, 6,804], provides a straightforward way to calculate the ionization potentials (IPs) as an one electron quantity. However, such an EKT-MP2 method often suffers from the negative occupation problem, failing to provide the complete IP spectra for a system of interest. Here a small positive number scheme is proposed to cure this problem so as to remove the associated unphysical results. In order to obtain an in-depth physical interpretation of the EKT-MP2 method, we introduce a Koopmans-type quantity, named KT-MP2, based on which the respective contribution from the relaxation and the correlation parts in the EKT-MP2 results are recognized. Furthermore, the close relationship between the EKT-MP2 method and the derivative approach of the MP2 energy with respect to the orbital occupation numbers [N. Q. Su and X. Xu, J. Chem. Theory Comput. 2015, 11, 4,677] is revealed. When these MP2-based methods are applied to a set of atoms and molecules, new insights are gained on the role played by the relaxation and the correlation effects in the electron ionization processes.

LncRNA KCNQ1OT1 knockdown inhibits viability, migration and epithelial-mesenchymal transition in human lens epithelial cells via miR-26a-5p/ITGAV/TGF-beta/Smad3 axis.

BACKGROUND: Long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) takes part in diabetic cataract progression. This research aims to analyze the function and mechanism of KCNQ1OT1 on viability, migration and epithelial-mesenchymal transition (EMT) in lens epithelial cells. METHODS: 20 diabetic cataract posterior lens capsule tissues and normal samples were collected. Lens epithelial cells (SRA01/04) were stimulated via high glucose (HG). The levels of KCNQ1OT1, miR-26a-5p, integrin αV (ITGAV), TGF-ß, Smad3 and phosphorylated (p)-Smad3 were measured via quantitative real-time polymerase chain reaction or Western blot. Cell viability, migration and EMT were analyzed via MTT, wound healing, transwell and Western blot assays. The target relationship between miR-26a-5p and KCNQ1OT1 or ITGAV was determined via luciferase reporter assay. RESULTS: KCNQ1OT1 was up-regulated and miR-26a-5p level was reduced in diabetic cataract tissues and HG-treated SRA01/04 cells. Silence of KCNQ1OT1 or miR-26a-5p up-regulation repressed cell viability, migration and EMT in SRA01/04 cells stimulated via HG. KCNQ1OT1 could target miR-26a-5p and controlled cell viability, migration and EMT via regulating miR-26a-5p. ITGAV was targeted via miR-26a-5p and positively regulated via KCNQ1OT1. ITGAV overexpression promoted cell viability, migration and EMT in HG-treated SRA01/04 cells, which were mitigated by KCNQ1OT1 silence. KCNQ1OT1 knockdown mitigated HG-induced the activation of TGF-ß/Smad3 signaling by regulating miR-26a-5p. CONCLUSION: KCNQ1OT1 knockdown represses cell viability, migration and EMT through miR-26a-5p/ITGAV/TGF-ß/Smad3 axis in SRA01/04 cells under HG condition, providing a new target for the treatment of diabetic cataract.

A correlation-relaxation-balanced direct method at the second order perturbation theory for accurate ionization potential predictions.

The development of a quasi-particle approach for an accurate yet efficient prediction of a complete ionization potential (IP) spectrum, from valence down to core electrons for the system of interest, is a long-cherished goal in quantum chemistry. Based on the physical understanding of the electron correlation and relaxation effects at the second order perturbation theory, we present here a correlation-relaxation-balanced direct method, dubbed CRB-MP2, via a parameter scaled scheme of the 2ph (two-particle, one-hole summation) and 2hp (two-hole, one-particle summation) terms. With almost no extra computational cost after a normal MP2 procedure, the CRB-MP2 method yields high quality valence and core IPs for a wide range of species. A direct approach for complete IP spectrum calculations with both computational accuracy and efficiency is therefore established.

Extended Koopmans' theorem in the adiabatic connection formalism: Applied to doubly hybrid density functionals.

A rigorous framework that combines the extended Koopmans' theorem (EKT) with the adiabatic connection (AC) formalism of density functional theory is developed here, namely, EKT-AC, to calculate the vertical ionization potentials (IPs) of molecular systems. When applied to the doubly hybrid density functional approximations (DH-DFAs), the EKT-DH approach is established for the B2PLYP-type DHs with one-parameter and two-parameters, as well as the XYG3-type DHs. Based on EKT-DH, an approximation of the KT type is introduced, leading to the KT-DH approach. The IP-condition that the calculated vertical IPs with EKT-DH or KT-DH are to reproduce the experimental IPs closely is applied to investigate the commonly used DH-DFAs for such a purpose and is utilized as a principle for DH-DFA developments. Considering the systematic improvements, as well as its numeric stability, we recommend the KT-B2GPPLYP approach as a pragmatic way for vertical IP calculations.

Retinal break associated with traumatic lens dislocation or subluxation requiring vitrectomy.

BACKGROUND: Both ectopia lentis and retinal injury are common results of blunt ocular trauma. Here, we investigated the incidence and characteristics of retinal breaks associated with ectopia lentis caused by blunt ocular trauma. METHODS: Patients who underwent pars plana vitrectomy to treat traumatic lens subluxation and dislocation were retrospectively reviewed. The incidence, characteristics, and outcomes of retinal breaks were analyzed. RESULTS: Forty-five eyes from 45 patients were included in the study. Seventeen eyes (37.7%) were complicated by retinal breaks or detachment, but only four (8.9%) were identified pre-operation. Our study revealed that retinal breaks were more frequently located at the superior (72.7%) and peripheral (81.8%) retina. All patients achieved anatomic recovery post-surgery. The eyes with and without retinal breaks did not differ significantly with respect to initial or final visual acuity. The final visual outcomes were independently and significantly associated with visual acuity at presentation (P = 0.001). CONCLUSIONS: Retinal breaks occurred in approximately one-third of patients with traumatic ectopia lentis and were difficult to observe pre-operation. Complete ophthalmic evaluation and timely intervention may help achieve favorable outcomes.

Altered Expression Profile of Circular RNAs in the Serum of Patients with Diabetic Retinopathy Revealed by Microarray.

PURPOSE: Diabetic retinopathy (DR) is the leading cause of blindness among working age adults. Circular RNAs (circRNAs) are a kind of noncoding RNAs that are involved in the development of some diseases. Here, we aimed to determine the possible role of circRNAs in the pathogenesis of DR by determining the expression profile of circRNAs in the serum of DR patients. METHODS: Nineteen subjects with type 2 diabetes mellitus with proliferative DR (T2DR), 15 subjects with type 2 diabetes mellitus without DR (T2DM), and 21 age-matched nondiabetic control subjects were included in the study. Expression profiles in the serum samples from 5 subjects of each group were studied by circular microarray and validated by quantitative real-time polymerase chain re- action (qRT-PCR) in another 40 subjects. Bioinformatic software was used to predict the microRNA response elements. RESULTS: Thirty circRNAs were significantly upregulated in the serum of T2DR patients compared with the serum from both T2DM and control patients. Further, the altered expression of 7 circRNAs (hsa_circRNA_063981, hsa_circRNA_ 404457, hsa_circRNA_100750, hsa_circRNA_406918, hsa_ circRNA_104387, hsa_circRNA_103410, and hsa_circRNA_ 100192) were verified by qRT-PCR. CONCLUSION: This study suggested a potential role of circRNAs in the pathogenesis of DR and provides novel molecular targets for clinical therapy.

Silencing Matrix Metalloproteinases 9 and 2 Inhibits Human Retinal Microvascular Endothelial Cell Invasion and Migration.

PURPOSE: Proliferative retinal angiogenesis may severely impair the retina. Previous studies have indicated that matrix metalloproteinase (MMP)-2 and MMP-9 play important roles in the process of retinal angiogenesis. In this study, we suppressed MMP-2 and MMP-9 expression with RNA interference (RNAi) and then observed the inhibitory effects on the invasion and migration of human retinal microvascular endothelial cells (HRMECs). METHODS: Small interfering RNAs against MMP-2 mRNA and MMP-9 mRNA were synthesized. After transfection, the MMP-2 and MMP-9 expression in HRMECs was examined by real-time polymerase chain reaction and Western blot analysis. Cell migration and invasion were measured with a migration assay and a scratch wound assay, respectively. RESULTS: RNAi against MMP-2 and MMP-9 successfully inhibited the mRNA and protein expression of MMP-2 and MMP-9 in HRMECs. MMP-2 and MMP-9 knockdown could inhibit the invasion and migration of HRMECs. CONCLUSIONS: These findings suggest that the RNAi approach towards MMP-2 and MMP-9 may be a potentially effective therapeutic method for the treatment of proliferative retinal angiogenesis.

Evaluation of anterior chamber morphology following scleral buckling with Pentacam.

PURPOSE: To evaluate anterior segment parameter changes following scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD) using the Pentacam Scheimpflug system. METHODS: Twenty-eight phakic eyes of 28 patients who underwent SB surgery for RDD were included. The anterior chamber volume (ACV), central anterior chamber depth (CACD), mean anterior chamber angle (ACA) and ACA in a specific position (buckle quadrant), and central corneal thickness (CCT) were evaluated preoperatively and at 1 day, 1 week, and 1 and 3 months postoperatively by an anterior Pentacam Scheimpflug method. RESULTS: The ACV parameters were significantly decreased compared with preoperative levels at 1 day after SB surgery (P = 0.0004), but had no significant differences at 1 week, and 1 and 3 months (P > 0.05). The mean intraocular pressure (IOP) at 1 day was significantly higher than the preoperative level, but no subsequent significant difference was noted between the preoperative IOP and that at 1 week and 1 and 3 months postoperatively (P > 0.05). The CCT at 1 day after surgery increased significantly (P = 0.0122) and subsequently returned to the normal level postoperatively at 1 week and remained stable until 3 months (P > 0.05). The degree of postoperative ACA displayed different changes in the different quadrants and there was a significant increase in the ACA of the buckle quadrants at 1 day (P < 0.0001), 1 week (P = 0.02), and 1 month (P = 0.0266) after surgery, returning to the normal level at 3 months. CONCLUSIONS: The changes of anterior chamber parameters after SB can be demonstrated by Pentacam both objectively and quantitatively. The ACV and CCT changes were mild and resumed their preoperative parameters after 1 week, while the increase of the ACA at the buckle quadrant returned to normal after 3 months. SB surgeries without encircling or conducted with radial buckling might decrease anterior chamber change.

[Supracapsular implantation with optic capture of posterior chamber intraocular lens in aphakic school-age children after traumatic cataract].

OBJECTIVE: To assess the clinical effects of supracapsular implantation with optic capture of the posterior chamber intraocular lens in school-age children with traumatic cataract. METHOD: It was a retrospective case series study. Thirteen cases (13 eyes) received posterior curvilinear capsulorhexis with optic capture of the posterior chamber intraocular lens. Pre- and post-operative visual acuities were recorded. Intra-o and post-operative complications were observed. The follow-up period ranged from 6 to 42 months. RESULTS: Implantation of optic capture of the posterior chamber intraocular lens was successfully performed in 13 eyes. The best-corrected-visual acuity ranged from 0.2 to 1.0. No optic axis opaque was found in 10 eyes with optic capture. The major complications of optic capture were lenticular precipitates and posterior synechia of the iris. Intraocular dislocation was found in one case two weeks after the operation. CONCLUSIONS: Supracapsular implantation with optic capture of the posterior chamber intraocular lens is safe and effective for the treatment of traumatic cataract in school-age children.

Symmetry Dilemma of Doubly Hybrid Density Functionals for Equilibrium Molecular Property Calculations.

In electronic structure theory, when an approximate wavefunction tends to artifactually break the symmetry of the exact Hamiltonian, the corresponding method is referred to as having a "symmetry dilemma" problem. Such types of artifacts were often reported when Hartree-Fock (HF) and the low-level post-HF methods were used, while the traditional Kohn-Sham density functional theory (KS-DFT) methods were usually found to be more resistant to this breakdown. In this work, we present a systematic study on the reliability of the doubly hybrid (DH) DFT methods for several violable cases. Almost all the commonly used B2PLYP-type (bDH) functionals are shown to have a severe "symmetry dilemma" problem and yield dramatically unreliable molecular properties, such as dipole moment, vibrational frequency, and static polarizability at the equilibrium geometry. A one-parameter bDH functional model study demonstrates that such a problem is a combined effect of the inappropriate portion of the HF exchange (over 50%) for the self-consistent field (SCF) calculation and the augmentation of the second-order perturbative contribution. It is remarkable that the XYG3-type (xDH) functionals show a good capability to resist the artifactual symmetry breaking and yield reliable molecular properties when the same critical cases are calculated. In the xDH, there are two functionals of different purposes, namely, the SCF functional and the energy functional, which have different amounts of the HF exchange and different portions of the correlation contributions. The success of the xDHs can be attributed to this flexibility in xDH construction to avoid using an improperly large portion of the HF exchange in the SCF functional. The insights gained in this work are of significance for the development of an improved DH functional.

Second-Order Analytic Derivatives for XYG3 Type of Doubly Hybrid Density Functionals: Theory, Implementation, and Application to Harmonic and Anharmonic Vibrational Frequency Calculations.

Analytic derivative methods in quantum chemistry are powerful tools for the calculation of molecular properties and simulation of chemical systems. While the derivatives of the well-established B2PLYP type of doubly hybrid (DH) density functionals can be generated by a straightforward combination between the Kohn-Sham density functional and the second-order perturbation theory (PT2), both of these two contributions have to be considered nonvariationally for the XYG3 type of DH functionals (xDHs). A total Lagrangian that includes both parts is therefore needed for the corresponding Z-vector equations for the first-order derivatives of xDHs. Starting from the differentiation of the Z-vector equations, a theory for the second-order derivatives for xDHs is developed here and is applied to the molecular harmonic and anharmonic vibrational frequency calculations. The results are generally of high quality, as compared to the well-established experimental and CCSD(T) counterparts. Further investigations on the fundamental frequency predictions prove the capability of the xDH functionals for an accurate calculation of spectroscopic properties for a wide range of medium-size molecules.

Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina.

Retinitis pigmentosa (RP) is a form of inherited retinal degenerative diseases that ultimately involves the macula, which is present in primates but not in the rodents. Therefore, creating nonhuman primate (NHP) models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the future. Here we applied adeno-associated virus (AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque (Macaca mulatta) to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate RP. Through a series of studies, we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression. More importantly, the mutant macaque retinae displayed clinical RP phenotypes, including photoreceptor degeneration, retinal thinning, abnormal rod subcellular structures, and reduced photoresponse. Therefore, we suggest somatic editing of the RHO gene is able to phenocopy RP, and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study.

A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness.

PURPOSE: To identify the gene mutation responsible for a previously described rat model of X-linked congenital stationary night blindness (CSNB). METHODS: Rat orthologous genes for Nyx and Cacna1f were isolated from retina through rapid amplification the cDNA ends (RACE) and examined for mutations. Electroretinograms were used to identify affected animals. RESULTS: The rat Nyx cDNA spans 1,971 nucleotides and encodes a protein of 476 amino acids (GenBank: DQ393414). The rat Cacna1f cDNA spans 6,076 nucleotides and encodes a protein of 1,980 amino acids (GenBank: DQ393415). A c.2941C>T (p.R981Stop) mutation in Cacna1f was found in affected rats. Immunochemistry study showed labeling for rod bipolar and horizontal cells were reduced in affect retinas. For affected rats, b-wave and oscillatory potentials of scotopic ERG were absent, and b-wave of photopic ERG was clear but obviously reduced. CONCLUSIONS: The Cacna1f mutation identified in the rat model of CSNB was predicted to lead to a protein product that is shortened by 999 amino acids, indicating that this is a model for the incomplete subtype of human X-linked CSNB (CSNB2). This rat model will be useful for defining the pathophysiological properties of this human disorder.

Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients.

AIM: To comprehensively analyze the risk factors of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS: A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope (UBM). Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS: There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60±3.62 vs 12.96±3.55, P<0.001), best-corrected visual acuity was worse [3.00 (2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and larger extent of retinal detachment (P<0.001) were significant and independent risk factors for developing CD. CONCLUSION: For CD in RRD, related factors include BCVA, IOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low IOP are significant and independent risk factors.

A potential spontaneous rat model of X-linked congenital stationary night blindness.

PURPOSE: To describe a possible spontaneous rat model of X-linked congenital stationary night blindness (CSNB). METHODS: Experimental animals were generated by mating the affected animal to normal rats, and from interbreeding littermates. To define the inheritance pattern, full-field electroretinograms (ERGs) were recorded from all progeny. RESULTS: During the course of other experiments, an affected male rat was identified by a reduced amplitude ERG b-wave. When this rat was mated to normal Sprague-Dawley rats, all of the F1 progeny had normal ERG waveforms. When F1 offspring were interbred, 51% of the male offspring had b-wave reductions while all female offspring had normal ERG waveforms. When F1 females were backcrossed to the original affected male, b-wave reductions were noted in both male and female offspring; overall, 46.8% of the backcross progeny exhibited a b-wave reduction. In affected animals, the b-wave was selectively affected as the a-wave appeared to retain normal amplitude and kinetics at 1-4 months old. Cone ERGs were significantly reduced in amplitude and somewhat delayed. Similar ERG results were also obtained under the same stimulus conditions from human patients with complete CSNB (CSNB1). CONCLUSIONS: The inheritance pattern is consistent with an X-linked recessive trait. The electrophysiological results suggest that this mutant rat line may provide another model for CSNB1.