• My Dashboard My Education Find an Ophthalmologist
  • Home
  • Coronavirus
  • For Ophthalmologists
    • Meetings
      • AAO 2022
        • Meeting Information
          • Past and Future Meetings
          • Mobile Meeting Guide
          • Contact Information
          • Annual Meeting News
          • Health and Safety
          • Policies and Disclaimers
        • Program
          • Program Highlights
          • Subspecialty Day
          • Virtual Meeting
          • Program Committees
          • CME
          • Meeting Archives
        • Expo
        • Registration
        • Hotels & Travel
          • Hotel Reservation Information
          • Chicago
          • International Attendees
          • Hotel Meeting Space
        • Presenter Central
          • Presenter Central
          • Abstract Selection Process
          • Submission Policies
          • Subject Classification/Topics
          • Instruction Courses and Skills Transfer Labs
          • Papers and Posters
          • Videos
          • Grand Rounds Symposium
          • Program Participant and Faculty Guidelines
          • Faculty Development Program
        • Exhibitors
          • Exhibitor Central
          • Exhibitor Portal Information
          • Exhibitor Prospectus
          • New Exhibiting Companies
          • Exhibitor Resources
          • International Exhibitors
          • Promotional Opportunities
          • Exhibitor Hotel Reservations
      • Mid-Year Forum
        • Registration and Travel
        • Congressional Advocacy Day
        • Advocacy Ambassador Program
        • Program
        • Schedule
        • Sponsored Attendees
        • News
      • Codequest
        • Codequest Instructors
        • Claim Codequest CME or CEU Credit
      • Eyecelerator
    • Clinical Education
      • COVID-19
      • Education
        • Browse All Education
        • Courses
        • Cases
        • Learning Plans
        • Interactive
        • Focal Points
        • Wills Eye Manual
        • Disease Reviews
        • Clinical Webinars
        • Diagnose This
        • Self-Assessments
        • Educational Centers
          • Glaucoma Education Center
          • Pediatric Ophthalmology Education Center
          • Laser Surgery Education Center
          • Myopia Resources
          • Oculofacial Plastic Surgery Center
          • Redmond Ethics Center
      • Journals
      • Guidelines
        • Browse All Practice Guidelines
        • Preferred Practice Patterns
        • Clinical Statements
        • Compendium Guidelines
        • Complementary Therapy Assessments
        • Medical Information Technology
        • Ophthalmic Technology Assessments
        • Patient Safety Statements
        • Choosing Wisely
        • Low Vision
        • Eye Care for Older Adults
        • Eye Disease Statistics
        • About the Hoskins Center
      • Video and Image Library
        • Browse All Videos
        • Clinical and Surgical Videos
        • Presentations and Lectures
        • 1-Minute Videos
        • Master Class Videos
        • Basic Skills Videos
        • Interviews
        • Images
        • Submit an Image
        • Submit a Video
      • Podcasts
        • Browse All Audio and Podcasts
        • Experts InSight
        • Ophthalmology Journal
      • News
        • Browse All Clinical News
        • Editors' Choice
        • Headlines
        • Current Insight
      • CME Central
        • Browse All CME Activities
        • Claim CME Credit and View Transcript
        • CME Planning Resources
        • Complete Your Financial Disclosure
        • Joint Sponsorship Portal
        • LEO Continuing Education Recognition Award
        • Safe ER/LA Opioid Prescribing
        • Check Your Industry Payment Records
      • MOC
      • Resident Education
        • Resident Education Home
        • Browse All Resident Content
          • Courses
          • Flashcards
          • Interactive Cases and Simulations
          • Videos
          • Webinars
        • OKAP and Board Exam Resources
          • OKAP Exam
          • Board Prep Resources
          • OKAP and Board Review Presentations
          • Study Flashcards
        • Cataract Master
        • Diversity and Inclusion Education
        • News and Advice from YO Info
        • Pediatric Ophthalmology Education Center
        • PGY-1 and PGY-2 Resources
        • Simulation in Resident Education
    • Membership
      • Join
      • Renew
      • Current Member
      • Volunteer
      • Physician Wellness
      • Member Directory
      • Member Obituaries
      • AAOE Membership
    • Advocacy
      • Advocacy News
      • Get Involved
        • Ways to Give
        • How to Get Involved
        • Congressional Advocacy
        • Support the Academy's Agenda
        • Research Legislation
        • Find Your Legislators
        • I Am an Advocate
        • Advocacy at Home
        • Advocate Tools
        • Best Practices for Advocating at Home
        • Social Media Toolkit
        • Letter to Editor
        • Town Hall Guide
        • Guide to Engaging With New Lawmakers
        • Resources
        • Attending a Political Fundraiser
      • OPHTHPAC
        • About Us
        • Join OPHTHPAC
        • OPHTHPAC Blog
      • Surgical Scope Fund
        • Support Surgery By Surgeons
        • Surgery By Surgeons Blog
    • Publications
      • EyeNet Magazine
        • Latest Issue
        • Archive
        • Subscribe
        • Advertise
        • Write For Us
        • Corporate Lunches
        • Contact
        • MIPS 2022
      • Focal Points
      • Ophthalmology
      • Ophthalmology Glaucoma
      • Ophthalmology Retina
      • YO Info
      • Scope
    • Subspecialties
      • Cataract/Anterior Segment
      • Comprehensive Ophthalmology
      • Cornea/External Disease
      • Glaucoma
      • Neuro-Ophthalmology/Orbit
      • Ocular Pathology/Oncology
      • Oculoplastics/Orbit
      • Pediatric Ophthalmology/Strabismus
      • Refractive Management/Intervention
      • Retina/Vitreous
      • Uveitis
    • IRIS Registry
      • About
      • Using the Registry
        • User Guide
        • Medicare Reporting
        • Maintenance of Certification
        • Non-EHR Reporting
      • Sign Up
        • Application Process
        • Why Participate
        • Once You've Applied: Getting Started
        • What Practices Are Saying About the Registry
      • Requirements
        • EHR Systems
        • Data & Technical Needs
      • Research
      • Registry Dashboard
      • News
      • Medicare & MIPS
    • Medicare Information
    • Diversity, Equity, and Inclusion
  • For Practice Management
    • Managing Your Practice
      • Managing Your Practice Topics
      • Coronavirus Resources
      • Reopening & Recovery
      • Practice Forms Library
      • Practice Management News and Advice
      • AAOE-Talk
      • Video Library
      • Ophthalmology Job Center
      • Benchmarking and Salary Tools
      • Academy Consultations
      • Consultant Directory
    • Coding
      • Coding Topics
      • Codequest Events
      • Ask the Coding Experts
      • Coding Updates and Resources
      • Coding for Injectable Drugs
      • EM Documentation
      • ICD-10-CM
      • Ophthalmic Coding Specialist (OCS) Exam
      • Retina
      • Savvy Coder
    • Webinars and Events
      • Annual Meeting
      • Codequest Courses
      • Mid-Year Forum
      • Webinar Recordings
    • IRIS Registry
      • Merit-Based Incentive Payment
    • Medicare and MIPS
      • MIPS
        • Quality
        • Promoting Interoperability
        • Improvement Activities
        • Cost
        • Avoid a Penalty
      • Resources
      • Medicare Participation Options
      • Medicare Advantage Plans
      • New Medicare Card
      • Provider Enrollment, Chain and Ownership System (PECOS)
    • Regulatory Compliance
      • HIPPA Resources
      • Office of Inspector General
      • Audits
      • OSHA
    • AAOE Membership
      • Join AAOE
      • Membership Benefits
      • Renew/Pay Dues
    • About AAOE
      • AAOE Board of Directors
      • AAOE Content Committee
      • Volunteer Opportunities
  • For Public & Patients
    • Eye Health A-Z
    • Symptoms
    • Glasses & Contacts
    • Tips & Prevention
    • News
    • Ask an Ophthalmologist
    • Patient Stories
    • No Cost Eye Exams
    • Español
      • A - Z de Salud Ocular
      • Síntomas
      • Anteojos y Lentes de Contacto
      • Consejos y Prevención
      • Noticias
      • Relatos de Pacientes
      • Exámenes de la vista sin costo
      • English
  • AAO 2022
    • Meeting Information
      • Past and Future Meetings
      • Mobile Meeting Guide
      • Contact Information
      • Annual Meeting News
      • Health and Safety
      • Policies and Disclaimers
    • Program
      • Program Highlights
      • Subspecialty Day
      • Virtual Meeting
      • Program Committees
      • CME
      • Meeting Archives
    • Expo
    • Registration
    • Hotels & Travel
      • Hotel Reservation Information
      • Chicago
      • International Attendees
      • Hotel Meeting Space
    • Presenter Central
      • Presenter Central
      • Abstract Selection Process
      • Submission Policies
      • Subject Classification/Topics
      • Instruction Courses and Skills Transfer Labs
      • Papers and Posters
      • Videos
      • Grand Rounds Symposium
      • Program Participant and Faculty Guidelines
      • Faculty Development Program
    • Exhibitors
      • Exhibitor Central
      • Exhibitor Portal Information
      • Exhibitor Prospectus
      • New Exhibiting Companies
      • Exhibitor Resources
      • International Exhibitors
      • Promotional Opportunities
      • Exhibitor Hotel Reservations
  • About
    • Who We Are
      • What We Do
      • About Ophthalmology
      • The Eye Care Team
      • Ethics and the Academy
      • History
      • Museum of Vision
      • Values
    • Governance
      • Council
      • Board of Trustees
      • Committees
      • Academy Past Presidents
      • Secretariats
      • Elections
      • Academy Blog
      • Academy Staff Leadership
    • Leadership Development
    • Awards
      • Laureate Recognition Award
      • Outstanding Advocate Award
      • Outstanding Humanitarian Service Award
      • International Blindness Prevention Award
      • Distinguished Service Award
      • Guests of Honor
      • Secretariat Award
      • Straatsma Award
      • Achievement Award Program
      • Artemis Award
      • EnergEYES Award
      • International Education Award
      • International Scholar Award
      • Commitment to Advocacy Award
      • Visionary Society Award
    • Financial Relationships
    • Policy Statements
    • Related Organizations
      • Subspecialty/Specialized Interest Society Directory
      • State Society Directory
      • Subspecialty/Specialized Interest Society Meetings
      • State Society Meetings
      • Resources for Societies
    • Year in Review
      • 2020 Year in Review
  • Foundation
    • About
      • 2020-2021 Annual Report
      • Annual Report Archives
      • News From the Chair
      • Foundation Staff
    • Our Impact
      • Partners for Sight
      • Donor Spotlights
      • Global Ophthalmic Community
      • Sponsorships
      • Patients and the Public
    • Giving Options
      • Our Supporters
      • Estate and Planned Giving
      • Ophthalmic Business Council
      • Parke Center Campaign
      • Minority Ophthalmology Mentoring Campaign
      • Museum of the Eye Campaign
    • Orbital Gala
      • Why Attend
      • Photo Recap
      • Corporate Support Opportunities
      • Tribute Gifts
      • Silent Auction
      • Corporate Sponsors
    • Donate
    • Museum of the Eye Campaign
      • Museum Supporters
  • Museum of the Eye
    • Visit
    • What's On
      • Museum Galleries
      • Special Exhibitions
      • Current Events
      • Past Events
    • Explore
      • Research and Resources
      • Collection Search
      • Previous Exhibits
      • Oral Histories
      • Biographies
    • Volunteer
    • Mailing List
    • Donate
    • About the Museum
      • Museum Blog
  • Young Ophthalmologists
    • YO Info
    • Learn to Bill
    • Engage with the Academy
  • Senior Ophthalmologists
    • Scope
    • Practice Transitions
  • International Ophthalmologists
    • Global Programs and Resources for National Societies
    • Awards
    • Global Outreach
  • Residents
  • Medical Students
×
Shop
Log In Create an Account
  • For Ophthalmologists
  • For Practice Management
  • For Public & Patients
  • Coronavirus
  • About
  • Foundation
  • Museum of the Eye
  • COVID-19
  • Journals
  • Education
    • Education
    • Courses
    • Cases
    • Learning Plans
    • Interactive
    • Focal Points
    • Wills Eye Manual
    • Disease Reviews
    • Clinical Webinars
    • Diagnose This
    • Self-Assessments
    • Education Centers
      • Glaucoma Education Center
      • Pediatric Ophthalmology Education Center
      • Laser Surgery Education Center
      • Oculofacial Plastic Surgery Center
      • Redmond Ethics Center
      • Myopia Resources
      • Thyroid Eye Disease Resources
  • Guidelines
    • Practice Guidelines
    • Preferred Practice Patterns
    • Clinical Statements
    • Ophthalmic Technology Assessments
    • Patient Safety Statements
    • Complementary Therapy Assessments
    • Compendium Guidelines
    • Medical Information Technology
    • Low Vision
    • Choosing Wisely
    • Eye Care for Older Adults
    • Eye Disease Statistics
    • About the Hoskins Center
    • Artificial Intelligence
    • Premium IOLs
    • Patient-Reported Outcomes with LASIK Symptoms and Satisfaction
  • Multimedia
    • Multimedia Library
    • Video
      • 1-Minute Videos
      • Presentations and Lectures
      • Master Class Videos
      • Basic Skills Videos
      • Clinical and Surgical Videos
      • Interviews
      • Resident Lectures
      • Submit a Video
      • YO Video Contest
    • Podcasts
      • Browse Podcast Archive
      • Experts InSight Podcast
      • Ophthalmology Journal Podcast
    • Images
      • Submit an Image
  • News
    • Clinical News
    • Editors' Choice
    • Headlines
    • Current Insight
  • CME
    • CME Central
    • Claim CME Credit and View Transcript
    • CME Planning Resources
    • Complete Your Financial Disclosure
    • Joint Sponsorship Portal
    • LEO Continuing Education Recognition Award
    • Safe ER/LA Opioid Prescribing
    • Check Your Industry Payment Records
  • MOC
  • Residents
    • Resident Education Home
    • Browse All Resident Content
      • Courses
      • Flashcards and Study Presentations
      • Interactive Cases and Simulations
      • Videos
      • Webinars
    • Cataract Master
    • Diversity and Inclusion Education
    • News and Advice from YO Info
    • OKAP and Board Exam Resources
      • OKAP Exam
      • Board Prep Resources
      • OKAP and Board Review Presentations
      • Study Flashcards
    • Pediatric Ophthalmology Education Center
    • PGY-1 and PGY-2 Resources
    • Resident Knowledge Exchange
    • Simulation in Resident Education
    • Clinical Education /
    • Book Excerpts /
    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    2 Fundamentals and Principles of Ophthalmology

    Part IV: Biochemistry and Metabolism

    Chapter 13: Retinal Pigment Epithelium

    Major Physiologic Roles of the RPE

    The RPE has a number of physiologic roles (Fig 13-3). Crucial among these functions are

    • vitamin A regeneration, which is integral to sustaining vision

    • phagocytosis of shed photoreceptor outer-segment discs

    • biological filter for the neurosensory retina through transport of necessary nutrients and ions to photoreceptor cells and removal of waste products from photoreceptors

      Figure 13-3 Physiologic functions of the RPE. Additional functions (not shown) include its role in synthesis and remodeling of the interphotoreceptor matrix, formation of the outer blood–retina barrier, and formation of the basal lamina of Bruch membrane. PEDF = pigment epithelium–derived factor; VEGF = vascular endothelial growth factor.

      (Illustration by Cyndie C.H. Wooley.)

    • absorption of scattered and out-of-focus light via pigmentation

    • adhesion of the retina

    • secretion of humoral and growth factors

    These functions are discussed briefly in the following sections. Other important functions subserved by the RPE include its role in synthesis and remodeling of the interphotoreceptor matrix, formation of the outer blood–retina barrier, and formation of the basal lamina of Bruch membrane.

    Vitamin A Regeneration

    The RPE, second only to the liver in its concentration of vitamin A, plays a major role in the uptake, storage, and mobilization of vitamin A. The RPE supplies the photoreceptor outer segments with vitamin A, which is tethered to rhodopsin in rods and to the 3 different cone opsins (red, green, and blue). Although the different opsins have specific absorption spectra, vitamin A changes its configuration identically in response to the particular wavelength of light (see Chapter 12).

    The basic function of the RPE cell is to generate 11-cis-retinal (also called 11-cis-retinaldehyde) (Fig 13-4). Light-induced activation of rhodopsin leads to isomerization of 11-cis-retinal to all-trans-retinal and initiates the phototransduction cascade. Light-activated rhodopsin releases all-trans-retinal and must bind with another 11-cis-retinal to be ready for activation by the next photon of light. The free all-trans-retinal isomer undergoes a series of enzymatic reactions, called the visual cycle or retinoid cycle, to regenerate 11-cis-retinal. The visual cycle ensures a steady supply of 11-cis-retinal for the opsins for maintaining vision and requires close interaction between the RPE and photoreceptor outer segments. Similar processes occur in all photoreceptors; the process specific to rods is discussed below.

    Free all-trans-retinal is cleared from the rod discs by ABCA4, an ATP-binding cassette (ABC) transporter protein. After transport from the rod discs to the cytosol of the outer segments, all-trans-retinal is enzymatically reduced to all-trans-retinol by retinol dehydrogenase. All-trans-retinol is rapidly released by photoreceptor cells to the interphotoreceptor matrix, where it binds to interphotoreceptor retinoid-binding protein (IRBP). RPE cells contain cellular retinol-binding protein 1 (CRBP1), which promotes the uptake of all-trans-retinol into the RPE. The RPE also obtains vitamin A from the blood, where it is complexed with retinol-binding protein (RBP) and transthyretin. Phagocytosis of shed photoreceptor outer-segment discs (see the following section) by the RPE also allows recycling of vitamin A.

    Within the RPE cells, CRBP1-bound all-trans-retinol is enzymatically esterified by lecithin retinol acyltransferase (LRAT). The resultant retinyl ester is hydrolyzed and isomerized to the 11-cis configuration by the retinoid isomerohydrolase RPE65. 11-cis-Retinol is then oxidized to 11-cis-retinal by 11-cis-retinol dehydrogenase. The newly formed 11-cis-retinal is released from RPE cells to the interphotoreceptor matrix. From there it is transported by IRBP (IRBP binds both retinol and retinal forms) to the photoreceptor outer-segment discs to generate another visual transduction cycle.

    Figure 13-4 The visual cycle (also known as retinoid cycle) involves a series of reactions in the photoreceptor outer segments and RPE to regenerate 11-cis-retinal (also known as 11-cis-retinaldehyde). 11-cis Retinal attaches to a lysine residue on rhodopsin. When the complex absorbs light, 11-cis-retinal transforms into all-trans-retinal via a process known as photo-isomerization. This induces a conformational change in the attached rhodopsin molecule, activating the second-messenger system and initiating the phototransduction cascade within the photoreceptor. The all-trans-retinal is shed from rhodopsin and transported by ABCA4 from the rod disc to the cytosol, where it is converted to all-trans-retinol. Then, all-trans-retinol is delivered to the RPE via interphotoreceptor retinoid-binding protein (IRBP), which acts as a shuttle and also shields the cell membranes from the membranolytic retinoid molecules. Once in the RPE, this molecule is esterified by lecithin retinol acyltransferase (LRAT). The resultant retinyl ester is converted to 11-cis-retinol by the isomerohydrolase RPE65. 11-cis-Retinol is then oxidized to 11-cis-retinal by retinol dehydrogenase (RDH) and shuttled back to the photoreceptor outer-segment discs by IRBP to participate in another visual cycle. ABCA4 = ATP-binding cassette transporter protein; Apo-opsin = apo-rhodopsin; CRBP1 = cellular retinol-binding protein 1; PR = photoreceptor; RAL = retinal; RBP = retinol-binding protein; RE = retinyl ester; ROL = retinol; TTR = transthyretin; VitA = vitamin A.

    (Modified with permission from Singh RSJ, Kim JE. Visual cycle modulation. In: Lim J, ed. Age-related Macular Degeneration. 3rd ed. Boca Raton, FL: CRC Press; 2012:330.)

    CLINICAL PEARL

    Because vitamin A intermediaries are membranolytic, they require shuttles or are esterified to protect the plasma membrane of the photoreceptors and RPE. Mutations in the genes that encode the corresponding shuttles and enzymes have been identified in many inherited retinal diseases. Mutations of the ABCR gene, which encodes the ABC transporter protein ABCA4, lead to Stargardt disease. Mutation of the retinoid isomerohydrolase RPE65 gene (RPE65), which encodes the RPE65 protein, causes Leber congenital amaurosis (LCA) (see Table 13-1). RPE65 isomerohydrolase is the target of an FDA-approved treatment that uses an adeno-associated virus to deliver the RPE65 gene to the RPE of patients with LCA.

    • Testa F, Maguire AM, Rossi S, et al. Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital amaurosis type 2. Ophthalmology. 2013;120(6):1283–1291.

    Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

  • Most Commented
    Loading, please wait...
    There are no comments available.
    Most Viewed
    Loading, please wait...
    Most Viewed content is not available.
  • The Academy Store
    2022-2023 Basic and Clinical Science Course, Complete Print Set
    2022-2023 Basic and Clinical Science Course, Complete eBook Set
    2022-2023 Basic and Clinical Science Course, Complete Print and eBook Set
    2022-2023 Basic and Clinical Science Course, Residency Print Set
    2022-2023 Basic and Clinical Science Course, Residency eBook Set
    2022-2023 Basic and Clinical Science Course Complete Set
    2022-2023 Basic and Clinical Science Course Residency Set
    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
    2022-2023 Basic and Clinical Science Course, Section 12: Retina and Vitreous
    2022-2023 Basic and Clinical Science Course, Section 13: Refractive Surgery
    The Technician Point System: How to Improve Practice Accountability and Bottom Line (Free Member Webinar)
    Transitioning Your Practice: Retiring, Selling or Buying a Practice (Free Member Webinar)
    2022 IRIS Registry (Intelligent Research in Sight) Preparation Kit
    Advances in Medical and Surgical Management: The 2022 Update on Glaucoma
    Presbyopia-Correcting IOLs
    2022 Codequest - Multistate (Recorded March 29)
    2022 Codequest Virtual (Multistate)
    Retina Patient Education Video Collection
    Cataract and Refractive Surgery Patient Education Video Collection
    Glaucoma Patient Education Video Collection
 
  • Contact Us
  • About the Academy
  • Jobs at the Academy
  • Financial Relationships with Industry
  • Medical Disclaimer
  • Privacy Policy
  • Terms of Service
  • Help
  • For Advertisers
  • For Media
  • Ophthalmology Job Center

OUR SITES

  • EyeWiki
  • International Society of Refractive Surgery

FOLLOW THE ACADEMY

Medical Professionals

  • Facebook
  • Twitter
  • LinkedIn
  • YouTube

Public & Patients

  • Facebook
  • Twitter
  • Instagram
  • YouTube

Museum of the Eye

  • Facebook
  • Twitter
  • Instagram
  • YouTube
  • Trip Advisor
  • Yelp
© American Academy of Ophthalmology 2022