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2.
Ophthalmology ; 120(9): 1745-55, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23683945

RESUMO

OBJECTIVE: To evaluate quantitative and qualitative differences in documentation of the ophthalmic examination between paper and electronic health record (EHR) systems. DESIGN: Comparative case series. PARTICIPANTS: One hundred fifty consecutive pairs of matched paper and EHR notes, documented by 3 attending ophthalmologist providers. METHODS: An academic ophthalmology department implemented an EHR system in 2006. Database queries were performed to identify cases in which the same problems were documented by the same provider on different dates, using paper versus EHR methods. This was done for 50 consecutive pairs of examinations in 3 different diseases: age-related macular degeneration (AMD), glaucoma, and pigmented choroidal lesions (PCLs). Quantitative measures were used to compare completeness of documenting the complete ophthalmologic examination, as well as disease-specific critical findings using paper versus an EHR system. Qualitative differences in paper versus EHR documentation were illustrated by selecting representative paired examples. MAIN OUTCOME MEASURES: (1) Documentation score, defined as the number of examination elements recorded for the slit-lamp examination, fundus examination, and complete ophthalmologic examination and for critical clinical findings for each disease. (2) Paired comparison of qualitative differences in paper versus EHR documentation. RESULTS: For all 3 diseases (AMD, glaucoma, PCL), the number of complete examination findings recorded was significantly lower with paper than the EHR system (P ≤ 0.004). Among the 3 individual examination sections (general, slit lamp, fundus) for the 3 diseases, 5 of the 9 possible combinations had significantly lower mean documentation scores with paper than EHR notes. For 2 of the 3 diseases, the number of critical clinical findings recorded was significantly lower using paper versus EHR notes (P ≤ 0.022). All (150/150) paper notes relied on graphical representations using annotated hand-drawn sketches, whereas no (0/150) EHR notes contained drawings. Instead, the EHR systems documented clinical findings using textual descriptions and interpretations. CONCLUSIONS: There were quantitative and qualitative differences in the nature of paper versus EHR documentation of ophthalmic findings in this study. The EHR notes included more complete documentation of examination elements using structured textual descriptions and interpretations, whereas paper notes used graphical representations of findings. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Doenças da Coroide/diagnóstico , Documentação/normas , Registros Eletrônicos de Saúde/normas , Glaucoma de Ângulo Aberto/diagnóstico , Degeneração Macular/diagnóstico , Oftalmologia , Papel , Idoso , Idoso de 80 Anos ou mais , Técnicas de Diagnóstico Oftalmológico , Documentação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico
3.
J Acad Ophthalmol (2017) ; 13(2): e200-e209, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37388852

RESUMO

Purpose This study aimed to evaluate trends in ophthalmology resident operative experience and the early impact of the novel coronavirus disease 2019 (COVID-19) pandemic. Design Present study is a retrospective analysis of the Accreditation Council for Graduate Medical Education (ACGME) Case Log System. Participants Anonymized graduating resident case logs from 2011 to 2020 academic years (AYs) were examined for this study. Methods Regression analysis for each procedure category was performed to identify trends between 2011 and 2019 AYs. Unpaired two-tailed t -test compared 2018 to 2019 and 2019 to 2020 AY's for each category surgeon (S) and as surgeon and assistant (S + A). Main Outcome Measures Mean and median cases as (S) and (S + A) during 2011 to 2019 AYs. Comparison between 2018 to 2019 and 2019 to 2020 AY's for each category as (S) and (S + A) to evaluate the impact of the COVID-19 pandemic. Results Total ophthalmology procedures as (S) rose from a mean of 479.6 to 601.3 ( p < 0.001; R 2 = 0.96; Δ/year = 16.9) and a median of 444 to 537 ( p < 0.001; R 2 = 0.97; Δ/year = 13.1). Total procedures as (S + A) rose from a mean of 698.1 to 768 ( p < 0.01; R 2 = 0.83; Δ/year = 9.07) and a median of 677 to 734 ( p < 0.05; R 2 = 0.61; Δ/year = 6.64). Cataract procedures as (S) rose from a mean of 152.8 to 208 ( p < 0.001; R 2 = 0.99; Δ/year = 7.98) and a median of 146 to 197 ( p < 0.001; R 2 = 0.97; Δ/year = 7.87). Cataract procedures as both (S + A) rose from a mean 231.4 to 268.7 ( p < 0.001; R 2 = 0.95; Δ/year = 5.5) and a median of 213 to 254 ( p < 0.001; R 2 = 0.93; Δ/year = 5.33). Between 2018 to 2019 and 2019 to 2020 AYs, the first pandemic year was associated with significant reductions in total procedures (601.3-533.7 [ p < 0.0001]) as (S) and 768.0 to 694.4 ( p < 0.0001) as (S + A), cataract surgery (208-162.2 [ p < 0.0001]) as (S) and 268.7 to 219.1 ( p < 0.0001) as (S + A), and glaucoma surgery (16.3-14.2 [ p = 0.0068]) as (S) and 25.6 to 22.6 ( p = 0.0063) as (S + A). Conclusion During 2011 to 2019 AYs, cataract, intravitreal injections, glaucoma, and total procedures increased significantly. During the early period of the COVID-19 pandemic (2019-2020 AY), national halting of elective procedures had a precipitous effect on resident cataract surgery experience to volumes similar to 2013 to 2014 AY where the mean was twice the current required minimum number. With few exceptions, other procedure volumes remained stable.

4.
Clin Ophthalmol ; 14: 2777-2782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061261

RESUMO

PURPOSE: Patients and physicians are often pleased when uncorrected visual acuity (UCVA) on post-operative day 1 (POD1) after cataract surgery is 20/20. Unfortunately, this UCVA does not always last. This article aims to investigate the relationship between excellent uncorrected visual acuity on post-operative day 1 and final post-operative UCVA after uncomplicated cataract surgery. PATIENTS AND METHODS: The medical records of patients who had undergone uncomplicated cataract surgery between 2012 and 2017 were assessed. UCVA on POD1 and final UCVA were obtained for patients who had a final best-corrected visual acuity of 20/20 or better. RESULTS: Of 309 patients with UCVA of 20/20 on POD 1, 62.4% maintained 20/20 and 87.4% maintained 20/25 or better as their final uncorrected visual outcome. Of 204 patients with UCVA of 20/25 on POD 1, 44.1% achieved 20/20 and 69.6% maintained 20/25 or better as their final uncorrected visual outcome. Patients with 20/20 UCVA on POD1 were more likely to have a better final UCVA compared with those who were 20/25 on POD1. Of the 531 patients with UCVA of 20/25 or better on POD1, 20% had final UCVA worse than 20/25 with 4% losing more than 2 lines for their final UCVA. CONCLUSION: The majority of patients with 20/20 UCVA on POD1 after cataract surgery maintained excellent UCVA as their final visual outcome. However, a significant percentage of these patients experienced a decrease in UCVA over the course of the postoperative period.

5.
Neuron ; 48(6): 987-99, 2005 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-16364902

RESUMO

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate numerous nonvisual phenomena, including entrainment of the circadian clock to light-dark cycles, pupillary light responsiveness, and light-regulated hormone release. We have applied multielectrode array recording to characterize murine ipRGCs. We find that all ipRGC photosensitivity is melanopsin dependent. At least three populations of ipRGCs are present in the postnatal day 8 (P8) murine retina: slow onset, sensitive, fast off (type I); slow onset, insensitive, slow off (type II); and rapid onset, sensitive, very slow off (type III). Recordings from adult rd/rd retinas reveal cells comparable to postnatal types II and III. Recordings from early postnatal retinas demonstrate intrinsic light responses from P0. Early light responses are transient and insensitive but by P6 show increased photosensitivity and persistence. These results demonstrate that ipRGCs are the first light-sensitive cells in the retina and suggest previously unappreciated diversity in this cell population.


Assuntos
Potenciais de Ação/fisiologia , Diferenciação Celular/fisiologia , Transdução de Sinal Luminoso/fisiologia , Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Potenciais de Ação/efeitos da radiação , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos da radiação , Eletrofisiologia/instrumentação , Eletrofisiologia/métodos , Luz , Transdução de Sinal Luminoso/efeitos da radiação , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Rede Nervosa/crescimento & desenvolvimento , Rede Nervosa/metabolismo , Rede Nervosa/efeitos da radiação , Técnicas de Cultura de Órgãos , Estimulação Luminosa , Tempo de Reação/fisiologia , Retina/metabolismo , Retina/efeitos da radiação , Células Ganglionares da Retina/classificação , Células Ganglionares da Retina/efeitos da radiação , Opsinas de Bastonetes/genética
6.
Invest Ophthalmol Vis Sci ; 48(3): 1268-75, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17325172

RESUMO

PURPOSE: To determine the relative contributions of inner and outer retinal photoreception to the pupillary light response. METHODS: Wild-type, retinal degenerate (rd/rd), and melanopsin mutant (opn4(-/-)) mice were tested for pupillary light responsiveness by video pupillometry before, during, and after exposure to supersaturating light intensities. Similar lighting protocols were used to probe responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) recorded with multielectrode arrays ex vivo. RESULTS: Both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (intrinsically photosensitive retinal ganglion cells [ipRGCs]) are sufficient to drive the pupillary light response in mice. After supersaturating light exposure, rather than bleaching or adapting, rd/rd mice showed paradoxical potentiation of responses to subsaturating light exposure. opn4(-/-) mice, in contrast, could not sustain pupillary constriction under continuous bright illumination, and showed desensitization after bright-light exposure. Both the intensity of light necessary to induce potentiation and the spectral sensitivity for sustained and potentiated responses differed from that necessary to trigger pupillary constriction, suggesting that photopotentiation is dependent on a pigment-state distinct from that triggering the pupillary light response itself. Multielectrode array recordings of ipRGCs from rd/rd retinas demonstrated persistent cell firing under continuous light exposure but did not show potentiation. CONCLUSIONS: Unique photoreceptive properties of intrinsically photosensitive RGCs confer resistance to bleaching and/or adaptation under continuous bright illumination to the pupillary light response and suggest the presence of a photopigment with multiple absorption states.


Assuntos
Luz , Células Fotorreceptoras de Vertebrados/fisiologia , Pupila/efeitos da radiação , Reflexo Pupilar/fisiologia , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/fisiologia , Animais , Eletrofisiologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Gravação em Vídeo
7.
PLoS Med ; 2(11): e333, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16250670

RESUMO

BACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat-/- mice increased approximately 2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness.


Assuntos
Aciltransferases/genética , Cegueira/tratamento farmacológico , Cegueira/genética , Terapia Genética , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Atrofia Óptica Hereditária de Leber/genética , Pró-Fármacos/farmacologia , Vitamina A/análogos & derivados , Adenoviridae/genética , Administração Oral , Animais , Modelos Animais de Doenças , Diterpenos , Vetores Genéticos , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Pupila/fisiologia , Pigmentos da Retina/análise , Ésteres de Retinil , Vitamina A/administração & dosagem , Vitamina A/farmacologia , Vitamina A/uso terapêutico
8.
J AAPOS ; 18(6): 584-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25456030

RESUMO

PURPOSE: To measure the effect of electronic health record (EHR) implementation on productivity and efficiency in the pediatric ophthalmology division at an academic medical center. METHODS: Four established providers were selected from the pediatric ophthalmology division at the Oregon Health & Science University Casey Eye Institute. Clinical volume was compared before and after EHR implementation for each provider. Time elapsed from chart open to completion (OTC time) and the proportion of charts completed during business hours were monitored for 3 years following implementation. RESULTS: Overall there was an 11% decrease in clinical volume following EHR implementation, which was not statistically significant (P = 0.18). The mean OTC time ranged from 5.5 to 28.3 hours among providers in this study, and trends over time were variable among the four providers. Forty-four percent of all charts were closed outside normal business hours (30% on weekdays, 14% on weekends). CONCLUSIONS: EHR implementation was associated with a negative impact on productivity and efficiency in our pediatric ophthalmology division.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Eficiência Organizacional/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Implementação de Plano de Saúde , Oftalmologia/estatística & dados numéricos , Pediatria , Criança , Feminino , Pessoal de Saúde , Humanos , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Estados Unidos
9.
JAMA Ophthalmol ; 132(5): 586-92, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24676217

RESUMO

IMPORTANCE: Although electronic health record (EHR) systems have potential benefits, such as improved safety and quality of care, most ophthalmology practices in the United States have not adopted these systems. Concerns persist regarding potential negative impacts on clinical workflow. In particular, the impact of EHR operating room (OR) management systems on clinical efficiency in the ophthalmic surgery setting is unknown. OBJECTIVE: To determine the impact of an EHR OR management system on intraoperative nursing documentation time, surgical volume, and staffing requirements. DESIGN, SETTING, AND PARTICIPANTS: For documentation time and circulating nurses per procedure, a prospective cohort design was used between January 10, 2012, and January 10, 2013. For surgical volume and overall staffing requirements, a case series design was used between January 29, 2011, and January 28, 2013. This study involved ophthalmic OR nurses (n = 13) and surgeons (n = 25) at an academic medical center. EXPOSURES: Electronic health record OR management system implementation. MAIN OUTCOMES AND MEASURES: (1) Documentation time (percentage of operating time documenting [POTD], absolute documentation time in minutes), (2) surgical volume (procedures/time), and (3) staffing requirements (full-time equivalents, circulating nurses/procedure). Outcomes were measured during a baseline period when paper documentation was used and during the early (first 3 months) and late (4-12 months) periods after EHR implementation. RESULTS: There was a worsening in total POTD in the early EHR period (83%) vs paper baseline (41%) (P < .001). This improved to baseline levels by the late EHR period (46%, P = .28), although POTD in the cataract group remained worse than at baseline (64%, P < .001). There was a worsening in absolute mean documentation time in the early EHR period (16.7 minutes) vs paper baseline (7.5 minutes) (P < .001). This improved in the late EHR period (9.2 minutes) but remained worse than in the paper baseline (P < .001). While cataract procedures required more circulating nurses in the early EHR (mean, 1.9 nurses/procedure) and late EHR (mean, 1.5 nurses/procedure) periods than in the paper baseline (mean, 1.0 nurses/procedure) (P < .001), overall staffing requirements and surgical volume were not significantly different between the periods. CONCLUSIONS AND RELEVANCE: Electronic health record OR management system implementation was associated with worsening of intraoperative nursing documentation time especially in shorter procedures. However, it is possible to implement an EHR OR management system without serious negative impacts on surgical volume and staffing requirements.


Assuntos
Centros Médicos Acadêmicos , Documentação/métodos , Registros Eletrônicos de Saúde/organização & administração , Salas Cirúrgicas/organização & administração , Oftalmologia/organização & administração , Admissão e Escalonamento de Pessoal/organização & administração , Melhoria de Qualidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Oregon , Estudos Prospectivos , Fatores de Tempo
10.
AMIA Annu Symp Proc ; 2013: 1195-204, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24551402

RESUMO

Efficiency and quality of documentation are critical in surgical settings because operating rooms are a major source of revenue, and because adverse events may have enormous consequences. Electronic health records (EHRs) have potential to impact surgical volume, quality, and documentation time. Ophthalmology is an ideal domain to examine these issues because procedures are high-throughput and demand efficient documentation. This time-motion study examines nursing documentation during implementation of an EHR operating room management system in an ophthalmology department. Key findings are: (1) EHR nursing documentation time was significantly worse during early implementation, but improved to a level near but slightly worse than paper baseline, (2) Mean documentation time varied significantly among nurses during early implementation, and (3) There was no decrease in operating room turnover time or surgical volume after implementation. These findings have important implications for ambulatory surgery departments planning EHR implementation, and for research in system design.


Assuntos
Documentação , Sistemas Computadorizados de Registros Médicos , Registros de Enfermagem , Sistemas de Informação em Salas Cirúrgicas/organização & administração , Procedimentos Cirúrgicos Oftalmológicos , Estudos de Tempo e Movimento , Registros Eletrônicos de Saúde , Salas Cirúrgicas/organização & administração
11.
Trans Am Ophthalmol Soc ; 111: 70-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24167326

RESUMO

PURPOSE: To evaluate three measures related to electronic health record (EHR) implementation: clinical volume, time requirements, and nature of clinical documentation. Comparison is made to baseline paper documentation. METHODS: An academic ophthalmology department implemented an EHR in 2006. A study population was defined of faculty providers who worked the 5 months before and after implementation. Clinical volumes, as well as time length for each patient encounter, were collected from the EHR reporting system. To directly compare time requirements, two faculty providers who utilized both paper and EHR systems completed time-motion logs to record the number of patients, clinic time, and nonclinic time to complete documentation. Faculty providers and databases were queried to identify patient records containing both paper and EHR notes, from which three cases were identified to illustrate representative documentation differences. RESULTS: Twenty-three faculty providers completed 120,490 clinical encounters during a 3-year study period. Compared to baseline clinical volume from 3 months pre-implementation, the post-implementation volume was 88% in quarter 1, 93% in year 1, 97% in year 2, and 97% in year 3. Among all encounters, 75% were completed within 1.7 days after beginning documentation. The mean total time per patient was 6.8 minutes longer with EHR than paper (P<.01). EHR documentation involved greater reliance on textual interpretation of clinical findings, whereas paper notes used more graphical representations, and EHR notes were longer and included automatically generated text. CONCLUSION: This EHR implementation was associated with increased documentation time, little or no increase in clinical volume, and changes in the nature of ophthalmic documentation.


Assuntos
Centros Médicos Acadêmicos , Documentação/métodos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Oftalmologia , Idoso , Eficiência Organizacional/normas , Registros Eletrônicos de Saúde/normas , Oftalmopatias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
12.
Invest Ophthalmol Vis Sci ; 53(1): 454-60, 2012 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-22159024

RESUMO

PURPOSE: Mice lacking rods and cones retain pupillary light reflexes that are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is necessary and sufficient for this nonvisual photoreception. The mammalian inner retina also expresses the potential blue light photopigments cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal degenerate mice, suggesting a role for cryptochrome in inner retinal photoreception. METHODS: Nonvisual photoreception (pupillary light responses, circadian entrainment, and in vitro sensitivity of intrinsically photosensitive retinal ganglion cells) were studied in wild-type, rd/rd, and circadian clock-mutant mice with and without rd/rd mutation. RESULTS: Loss of cryptochrome in retinal degenerate mice reduces the sensitivity of the pupillary light response at all wavelengths but does not alter the form of the action spectrum, suggesting that cryptochrome does not function as a photopigment in the inner retina. The authors compounded the rd/rd retinal degeneration mutation with mutations in other essential circadian clock genes, mPeriod and Bmal1. Both mPeriod1⁻/⁻; mPeriod2⁻/⁻;rd/rd and Bmal1⁻/⁻;rd/rd mice showed significantly lower pupillary light sensitivity than rd/rd mice alone. A moderate amplitude (0.5 log) circadian rhythm of pupillary light responsiveness was observed in rd/rd mice. Multielectrode array recordings of ipRGC responses of mCryptochrome1⁻/⁻;mCryptochrome2⁻/⁻ and mPeriod1⁻/⁻;mPeriod2⁻/⁻ mice showed minimal sensitivity decrement compared with wild-type animals. mCryptochrome1⁻/⁻;mCryptochrome2⁻/⁻;rd/rd, mPeriod1⁻/⁻;mPeriod2⁻/⁻;rd/rd and Bmal1⁻/⁻;rd/rd mice all showed comparable weak behavioral synchronization to a 12-hour light/12-hour dark cycle. CONCLUSIONS: The effect of cryptochrome loss on nonvisual photoreception is due to loss of the circadian clock nonspecifically. The circadian clock modulates the sensitivity of nonvisual photoreception.


Assuntos
Relógios Circadianos/fisiologia , Reflexo Pupilar/fisiologia , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia , Animais , Ritmo Circadiano/fisiologia , Criptocromos/genética , Feminino , Luz , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Estimulação Luminosa , Degeneração Retiniana/genética
13.
Invest Ophthalmol Vis Sci ; 53(8): 4644-56, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22562504

RESUMO

PURPOSE: We characterize the in vivo changes over time in the retinal structure of wild-type mice alongside two lines of mice deficient in the ß-subunit of phosphodiesterase (rd1 and rd10 mice) using spectral domain optical coherence tomography (SD-OCT). METHODS: SD-OCT images were obtained using the Bioptigen spectral domain ophthalmic imaging system (SDOIS). Wild-type C57BL/6J, rd1 and rd10 mice ranging in age from P14 to P206 were sedated with 1% isoflurane. Horizontal and vertical linear scans through the optic nerve, and annular scans around the optic nerve were obtained. RESULTS: SD-OCT imaging of wild-type mice demonstrated visibility of the inner segment/outer segment (IS/OS) junction, external limiting membrane (ELM), outer nuclear layer (ONL), and outer plexiform layer (OPL). At P14, most rd10 mice exhibited normal SD-OCT profiles, but some displayed changes in the IS/OS junction. At the same time point, rd1 mice had severe outer retinal degeneration. In rd10 mice, imaging revealed loss of the IS/OS junction by P18, hyperreflective changes in the ONL at P20, hyperreflective vitreous opacities, and shallow separation of the neural retina from the RPE. Retinal separations were not observed in rd1 mice. Segmentation analysis in wild-type mice demonstrated relatively little variability between animals, while in rd10 and rd1 mice there was a steady decline in outer retinal thickness. Histologic studies demonstrated correlation of retinal features with those seen on SD-OCT scans. Segmentation analysis provides a quantitative and reproducible method for measuring in vivo retinal changes in mice. CONCLUSIONS: SD-OCT provides a non-invasive method of following long-term retinal changes in mice in vivo. Although rd10 and rd1 mice have mutations in the same gene, they demonstrate significantly different features on SD-OCT.


Assuntos
Diester Fosfórico Hidrolases/deficiência , Degeneração Retiniana/patologia , Tomografia de Coerência Óptica/métodos , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Diester Fosfórico Hidrolases/genética , Degeneração Retiniana/enzimologia , Epitélio Pigmentado da Retina
14.
Proc Natl Acad Sci U S A ; 103(27): 10426-10431, 2006 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-16788071

RESUMO

Mice lacking the visual cycle enzymes RPE65 or lecithin-retinol acyl transferase (Lrat) have pupillary light responses (PLR) that are less sensitive than those of mice with outer retinal degeneration (rd/rd or rdta). Inner retinal photoresponses are mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting that the melanopsin-dependent photocycle utilizes RPE65 and Lrat. To test this hypothesis, we generated rpe65(-/-); rdta and lrat(-/-); rd/rd mutant mice. Unexpectedly, both rpe65(-/-); rdta and lrat(-/-); rd/rd mice demonstrate paradoxically increased PLR photosensitivity compared with mice mutant in visual cycle enzymes alone. Acute pharmacologic inhibition of the visual cycle of melanopsin-deficient mice with all-trans-retinylamine results in a near-total loss of PLR sensitivity, whereas treatment of rd/rd mice has no effect, demonstrating that the inner retina does not require the visual cycle. Treatment of rpe65(-/-); rdta with 9-cis-retinal partially restores PLR sensitivity. Photic sensitivity in P8 rpe65(-/-) and lrat(-/-) ipRGCs is intact as measured by ex vivo multielectrode array recording. These results demonstrate that the melanopsin-dependent ipRGC photocycle is independent of the visual retinoid cycle.


Assuntos
Retina/fisiologia , Células Ganglionares da Retina/metabolismo , Retinoides/metabolismo , Visão Ocular/fisiologia , Animais , Proteínas de Transporte , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Luz , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Pupila , Retina/patologia , Opsinas de Bastonetes/genética , Opsinas de Bastonetes/metabolismo , cis-trans-Isomerases
15.
Science ; 306(5693): 129-31, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15459395

RESUMO

The embryonic chicken iris constricts to light ex vivo, but with characteristics atypical of visual phototransduction. The chick iris was most sensitive to short-wavelength light, demonstrating an action spectrum consistent with cryptochrome rather than with opsin pigments. Pupillary responses did not attenuate after saturating light exposure, but showed paradoxical potentiation. Iris photosensitivity was not affected by retinoid depletion or inhibitors of visual phototransduction. Knockdown of cryptochrome expression, but not of melanopsin expression, decreased iris photosensitivity. These data characterize a non-opsin photoreception mechanism in a vertebrate eye and suggest a conserved photoreceptive role for cryptochromes in vertebrates.


Assuntos
Flavoproteínas/fisiologia , Iris/embriologia , Iris/fisiologia , Luz , Animais , Embrião de Galinha , Criptocromos , Flavoproteínas/genética , Transdução de Sinal Luminoso/efeitos dos fármacos , RNA Interferente Pequeno , Reflexo Pupilar , Retinoides/análise , Retinoides/fisiologia , Opsinas de Bastonetes/genética , Opsinas de Bastonetes/fisiologia , Raios Ultravioleta
16.
J Biol Chem ; 279(11): 10422-32, 2004 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-14684738

RESUMO

Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are approximately 35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.


Assuntos
Aciltransferases/fisiologia , Ésteres/metabolismo , Olho/metabolismo , Fígado/metabolismo , Aciltransferases/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Cromatografia Líquida de Alta Pressão , DNA Complementar/metabolismo , Eletrorretinografia , Vetores Genéticos , Genótipo , Homozigoto , Imuno-Histoquímica , Cinética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Microscopia Eletrônica , Microscopia de Fluorescência , Modelos Genéticos , Fótons , Retina/ultraestrutura , Retinoides/metabolismo , Rodopsina/química , Rodopsina/metabolismo , Fatores de Tempo , Distribuição Tecidual
17.
Science ; 301(5632): 525-7, 2003 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-12829787

RESUMO

Although mice lacking rod and cone photoreceptors are blind, they retain many eye-mediated responses to light, possibly through photosensitive retinal ganglion cells. These cells express melanopsin, a photopigment that confers this photosensitivity. Mice lacking melanopsin still retain nonvisual photoreception, suggesting that rods and cones could operate in this capacity. We observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light. This indicates the importance of both nonvisual and classical visual photoreceptor systems for nonvisual photic responses in mammals.


Assuntos
Cegueira/fisiopatologia , Transdução de Sinal Luminoso , Luz , Células Fotorreceptoras de Vertebrados/fisiologia , Opsinas de Bastonetes/fisiologia , Animais , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Cegueira/genética , Ritmo Circadiano , Camundongos , Camundongos Endogâmicos C3H , Atividade Motora , Reflexo Pupilar , Degeneração Retiniana/genética , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/deficiência , Opsinas de Bastonetes/genética , Transdução de Sinais , Núcleo Supraquiasmático/fisiologia
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