OPTO30007.docx

**OPTO30007 -- NOTES SM2 2024** **[LECTURE 1 -- WEEK 1 -- ANATOMY OF THE EYE]** **Problem 1:** - 47yo lady experiences deep boring pain in the left eye whilst watching movie - Sees haloes - (Vision below 6/12 are not suitable for driving), the lady has a vision of 6/6 in the left...

**OPTO30007 -- NOTES SM2 2024** **[LECTURE 1 -- WEEK 1 -- ANATOMY OF THE EYE]** **Problem 1:** - 47yo lady experiences deep boring pain in the left eye whilst watching movie - Sees haloes - (Vision below 6/12 are not suitable for driving), the lady has a vision of 6/6 in the left eye Examination = narrow anterior chamber angle (a shallowing of drainage angle in the front part or anterior chamber of the eye) **this menas that the angle between the iris and the cornea is narrow**.... **what does this mean for the lady?** **\ ** **(EYE)** **Outer coat** - **Cornea and sclera** - FUNCTION; *Transparency & Strength* **Middle coat** - **Ciliary body,** iris, choroid - FUNCTION*; 1. Aqueous humour production, 2., Accommodation* (focusing) 1. *Aqueous humour production* - Important for the health of the Lense and cornea - Creates intraocular pressure - Formed by ciliary epithelial cells 2. Accommodation (focusing) - Ligaments attach to ciliary processes - Involves contraction of the ciliary muscle **Inner Coat** - **Retina** - Optic nerve / optic disk - Fovea - Macula (are in which the fovea sits) - Posterior pole - Ora serrata **[HOW DO WE SEE?]** - There are factors that can limit visual acuity, being neural factors and optical factors. 1. **Neural factors** 2. **[Optical factors ]** - Pupil size - Clarity of optical media (cataracts, corneal opacities etc.) - Refractive errors (blur) -- due to; myopia, hypermetropia, astigmatism, presbyopia. **In terms of optical factors, there are multiple which impact vision in general:** a. **Cornea / tears:** - **Emmetropia --** where the refractive state of an eye in which paralleled rays of light entering the eye are focused on the retina EXACTLY, creating a crisp image perceived in focus. b. **Axial length of the eye determines power** (axial length is the length of the eye from the front to the back) - **Myopia --** short sightedness, where objects close look clear but far out are blurry - eye growth determines refractive state **Myopia,** although for short sightedness, is formed with a oblong (long) eye shape. - **Hypermetropia --** long sightedness, where objects far away look clear but up-close look burry. - **Hypermetropia**, although for long distance, Is formed with a smaller circle eye (opposite of oblong). c. **Variable focus due to crystalline lens:** - Balloon suspended in donut (ciliary) muscle - Thickens with age and less plastic - **Presbyopia** is loss of near focusing ability, at ages 40-45 -- need reading glasses. A diagram of different objects Description automatically generated **-THE NEURAL RETINA-** **=\> Contains 6 neurons:** 1\. HCs 2\. BCs 3\. ACs 4\. GCs 5\. Rods 6\. Cones **[THE NEURONAL LAYERS OF THE EYE ]** - There are 3 different neuronal layers 1. **Outer nuclear layer (ONL)** 2. **Inner nuclear layer (INL)** 3. **Ganglion cell layer (GCL)** **In the [INL] (inner nuclear layer)** - Contains the cell bodies of **horizontal, bipolar and amacrine** cells - Contains Müller cells **BIPOLAR CELLS** in INL: - Important in 'through' pathway - 10 different types of bipolar cells - 1 x rod bipolar cells - 9 x cone bipolar cells - Important for spatial vision and colour vision **Lateral inhibition** INL**: HORIZONTAL CELLS** - Input from photoreceptors - Provide output onto photoreceptors - Release inhibitory neurotransmitter GABA - Respond to light by hyperpolarizing **AMACRINE CELLS** in INL: - Many different types - Have no axons (axon less) - Important in lateral inhibition like horizontal cells - Release inhibitory neurotransmitters like glycine & GABA, often co-express more than one neurotransmitter. **[GANGLION CELL LAYER (GCL)]** - Cell bodies of GCs and some displaced amacrine cells live in the ganglion cell layer - Ganglion cells are the main output neuron of the retina (many different types: ON, OFF, M & P) - RGCs release Rtamate - RGCs fire action potentials  **OPTIMIZING VISION: Retinal Structure** **[Macula]** - Defined by where pigment lies in the retina (where the fovea is), but retinal layers are 'pushed' to the side - 3mm diameter - Exists no cells or processes to impede light transfer. - The central avascular zone is the optimized vision zone. **[OPTIC NERVE ]** - Formed by axons of ganglion cells as they exit the retina to pass visual information to higher cortical areas Note: Lamina cribosa is the area in which the ganglion axons begin to descend into one thick optical nerve, coming from the retina:  **[THE VISUAL PATHWAY BEYOND TRHE RETINA]** 1. RGCs go to lateral geniculate nucleus (LGN -- in thalamus) 2. 55% GC fibres cross at the optic chiasm 3. Cortical cells need stimulation from both eyes to develop properly. If not, **amblyopia** can form (reduced vision in one eye caused by abnormal visual development early in life) caused from... in difference in refractive state, turned eye (squint), congenital cataract or from lid pathology abnormality **[Glaucoma ]** - A name for a group of eye diseases where vision is lost due to damage to the optic nerve, typically irreversible vision loss. - **Types:** 1. Angle closure, 2. Angle open - **Treatment:** preventing RGC loss **SUMMARY OF LECTURE:** 1. Retina contains 3 neuronal layers (ONL, INL, GCL) 2. Retina contains 2 synaptic layers (OPL & IPL -- outer plexiform layer and inner plexiform layer) 3. OPL consists of connections among PRCs, BCs and HCs 4. IPL consists of connections among BCs, ACs and GCs. 5. For vision at high light levels: - Visual acuity is highest at the fovea - Depends on density of cones - Avascular fovea **[LECTURE 2 -- WEEK 1 -- THE RETINA 2: PHOTORECEPTORS]** **Lecture concept:** *What happened when light hits the retina?* **Problem 1:** - 45-year-old lady - Has trouble seeing at night - Trips over her children's toys - Has had many car accidents over the last 2 years - Can read OK - In a photo taken of Joan's fundus (**fundus** -- is the inside, back surface of the eye), it shows many black spots that hinder the fundus' natural colouration. **What does this mean for the lady?\...**  **THE RELATIONSHIP BETWEEN OUTER SEGMENT DISCS AND RHODOPSIN/OPSINS** - Both rod and cone cells utilize their outer segment discs to house light-sensitive molecules -- rhodopsin in rods and many different types of opsins in cones. - **RODS:** the tip (actual rod part) of the rod is known as the outer segment, and it is where rhodopsin molecules are housed, molecules which are photopigments. It consists of a protein called an opsin, bound with a light-sensitive molecule called 11-*cis* retinal. - *When light enters eye and reaches the retina, it is absorbed by the rhodopsin molecules, triggering a biochemical cascade that leads to changes in membrane potential and ultimately to the generation of neural signals.* - **CONES:** the actual cone tip of the cone is where opsins are housed, which can vary unlike rhodopsin, to different types like red, green and blue cones. -- opsin proteins are sensitive to different wavelengths of light - *Different cones respond to different types of wavelengths of light due to the presence of different opsins in their outer segment discs.* How do photo receptors respond to light? - *Photoreceptors are **hyperpolarized** by light.* - *Respond to light with graded changes in membrane potential (not action potentials)*  **[HOW DO PHOTORECEPTORS RECOVER]** **[FROM LIGHT? ]** 1. **[cGMP Control ]** - cGMP controls the ion channels - cGMP is continuously produced by ***guancylate cyclase*** (dependent on calcium levels) 2. **[Restoration of rhodopsin ]** - Activated rhodopsin is rapidly phosphorylated by ***rhodopsin kinase*** - This allows binding of **arrestin** to **phosphorylated rhodopsin.** - ***Bound arrestin prevents activated rhodopsin binding to transducin*** **[RETINITIS PIGMENTOSA]** - Genetic disorder - Creates tunnel vision - Is formed by a genetic defect in rhodopsin or proteins involved in phototransduction - Is characterised by degeneration of the retina - Degeneration of photoreceptor cells (rods and cones) leading to vision loss over time - Please explain Retinitis pigmentosa, and talk about its genetic defect in rhodopsin/proteins involved in phototransduction. Talk about how it creates tunnel vision. Thanks **[LECTURE 3 -- WEEK 2 -- THE RETINA 3: PARALLEL PATHWAYS ]** **Lecture concept:** *How is information from photoreceptors carried to downstream neurons?* **Problem 1: Monica** - Woman aged 65 - Noticed a disturbance in her vision - Water splashing in front of her left eye - 'Flickering lights' - Trips over her grandchildren's toys - Husband concerned about her driving - Vision 6/9, 6/12 - Good health Grade 3 Melanoma exercised 4 years ago {Lymph nodes +ve} **Why is this lady having trouble seeing?** **[PROCESSING VISUAL INFORMATION]** **[(BIPOLAR CELLS)]** - 2 different types of bipolar cells exist: - Both of which are meant to transmit signals from photoreceptors to ganglion cells - IT IS IMPORTANT TO REMEMBER THAT THE PRESENCE OF LIGHT & GLUTAMATE ON OFF/ON BCs PRODUCE DIFFERENT OUTCOMES, WHERE GLUTAMATE PRESNECE CAN BE HYPERPOLARISING OR DFEPOLARISING DEPENDANT ON LIGHT PRESENCE. ONN BCs when light hyperpolarises it. **[GANGLION CELLS]** - Output neurons of the retina - Many different types of cells (**M ganglion cells & P ganglion cells),** they both encode different types of visual information - Bipolar cells synapse with ganglion cells - **Ganglion cells can be ON or OFF types** - **ON BCs can only synapse with ON GCs**, and the same goes for OFF BC/GC. - **Communication between BC and GCs** is done via iGluRs such as NMDA, AMPA, and Kainate receptors. **[GC Function]**  **WHAT WAS WRONG WITH MONICA?** **[LECTURE 4 -- WEEK 2 -- THE RETINA 4: ROLE OF AMACRINE CELLS ]** **Lecture concept:** *What do amacrine cells do?* **Problem 1: What's wrong with baby Jane?** - Jane is a 10-year-old twin - At 3mo of age, father noticed horizontal eye movements (quivering eye movements) - **Examination:** bilateral nystagmus - Brain imaging all normal - Genetic testing: FRMD7 mutation (on X chromosome) **Why is this child having trouble seeing?** **[TYPES OF AMACRINE CELLS: ]** - Roughly 22 types - **Neurotransmitters** used - All contain Gaba or glycine - Some also contain Ach, Dopamine, neuropeptides **\[Amacrine cell inputs\]\ \*** Amacrine cells modify bipolar cell response - I.e., modify the retinal 'though' signal \[**Amacrine cell functions\]** - Amacrine cells release GABA and glycine onto bipolar cells and ganglion cells, 'fine tuning' the 'through' response. - **In terms of the rods and cones,** all cone bipolar cells synapse onto ganglion cells, however **rod bipolar cells** only synapse with amacrine cells. - **In light,** cones signal to bipolar cells, while at **low light level** the cones are not sensitive enough to signal, and so the rods signal to bipolar cells. - **Rod bipolar cells receives input from ONLY rods, where they express mGluR6 receptors, and depolarize when light falls on the retina.**  **[SACs/SBACs' directionally tuned inhibition]** - This mechanism describes the ensuring that SBACs provide inhibitory input to DSGCs only when motion is detected in the null direction, thereby enhancing the direction selectivity of DSGCs, and providing accurate motion detection in the visual system. - **Calcium responses:** SBAC dendrites exhibit varying calcium responses along their length, the signal intensity (amount of calcium released) depends on the direction of the stimulus. - **GABA release --** is the inhibitory neurotransmitter which is released when the stimulus moves form the soma (cell body) outward along the dendrite (**in a centrifugal direction**), but **NOT** when it moved toward the soma (**centripetal direction**). **THEREFORE,** - GABAergric inputs onto DSGCs come from SBAC dendrites that are orientated in the null direction. **Why Care About Motion Detection?** - **DSGCs** target 3 major pathways/regions of the brain: 1. **LGN -- Lateral Geniculate Nucleus** - Is relay centre in thalamus for visual information from retina to visual cortex - It processes motion signals and contributes to the perception of movement, enabling the brain to interpret dynamic visual scenes 2. **Superior Colliculus** - Involved in orienting movements of the eyes and head towards stimuli - Helps coordinate rapid eye movements (saccades) to track moving objects, facilitating attention and focus on relevant visual information. 3. **Accessory optic nucleus** - Involved in stabilizing the visual field during head movements - Process motion information to adjust eye movements and maintain stable vision, crucial for navigating the environment. **\ ** **[LECTURE 5 -- WEEK 2 -- THE RETINA 5: ROLE OF GANGLION CELLS ]** **Lecture concept:** *Types of ganglion cells and their roles.* **[COLOUR DISCRIMINATION ]** - **Within the eye, there are more red cones, then green cones, then blue cones** **There are:** 1. Blue cones: respond well to wavelengths 430 2. Green cone: respond well to wavelengths 530 3. Red cones: respond well to wavelengths 560 **[Colour Comparisons by RGCs (retinal ganglion cells)]** - Midget ganglion cells exhibit a colour opponent centre-surround surface, with the bullseye being the best reaction for ON GCs, and the surrounding area around the bullseye being the best place for reaction for the OFFS GCs. - *Some midget ganglion cells are excited by red falling on their centre and inhibited by green falling the surround (peripheral).* - *Others are excited by blue or yellow lights falling on their receptor field centre.* - Colour perceived is determined by the activity of ganglion cells. **[FUNCTION 1 of ipGCs: Concentral Pupil Response ]** - When light is shone in one eye, it restricts both the eye that is being shone with light and the remaining eye (both eyes) - When the **sphincter puillae** restricts, the pupil restricts. - So when light is shone in the eye, an intracellular circuit will result in either the constriction of the **sphincter pupillae** muscles, or the relaxation of the **dilator pupillae** muscles.  **So, what is the pathway of photosensitive GCs in a pupil response from shining light?** 1. **Pathway involves** the **Melanopsin GCs** projecting to the **Optical Pretectal Nucleus (OPN)** which is a pathway that **DOES NOT** cross at the optic chiasm, but stays to its' own respective 'eye lane'. Just before the LGN, the axon turns inward to project to the **Pretectal nucleus.** 2. This axon projects to the Pretectal nucleus which then sends a **neuron** projected to the **Edinger Westfal nucleus** in the **midbrain** on its own side and the opposite side **as well.** The Edinger Westfal nucleus is the parasympathetic innervation to the eye. 3. The **Edinger Westfal Nucleus** then send a neuron axon back to the **iris of the eye,** which is what allows for the **constriction and relaxation of muscles within the eye for the pupil response IN BOTH EYES.** - **THIS IS WHY WHEN YOU SHINE LIGHT INTO OTHER EYE, YOU CAUSE CONSTRICTION OF BOTH EYES.** - Therefore, the intrinsically photoreceptive GCs are very important in the constriction and relaxing of the pupil REGARDLESS of photoreceptors. **[FUNCTION 2 of ipGCs: Circadian Rhythm]** ipGCs target the **Superchiasmatic nucleus** of the **thalamus.** - Contains many nuclei that automate the *unconscious functioning* of the body, such as **sleep & mood**. **[LECTURE 6 -- WEEK 3 -- WHY DO WE NEED VISUAL ADAPTATIAN? ]** **Lecture concept:** *Our vision depends on our ability to detect small differences or changes in:* - *Intensity* - *Position* - *Colour* *...where this ability must be maintained under different light levels* - *Sunrise to sunset* [What is **adaptation** in the visual system?] - *Where the visual system adjusts its performance to changes in light levels (e.g ambient). Adaptation acts to match the limited neuronal response range to the visual input range.* - Most of the work is done by the **scotopic (rods) & photopic (cones)** systems. **{ VISUAL ADPATION }** **Weber's Law:** 'The minimum increase of stimulus which will produce a perceptible increase of sensation is proportional to the pre-existent stimulus". - The Lowest threshold in terms of illuminance adaption ability is greater for cones than it is for rods, although cones adapt faster than rods when the light is initially shone onto the retina. A diagram of a rose Description automatically generated **Rod Adaption:** Rods adapt are restricted range of intensity before they saturate (1-2 log units) (so they reach saturation). Yet, they are still able to respond in backgrounds of moderate intensity, and quite well in red lighting. **Cone Adaptation:** Adapt over a great range of intensities, and DO NOT REACH saturation.  **The GCAPs & Recoverin** are shared between rods and also cones. - **CNG** channel proteins (the proteins on the GCPAs that regulate Ca2+ binding) For rods: *Cna1/Cnb1* For cones: *Cnga3/Cngb3* - In Cones the 11-cis retinal is recycled by RPE cells and Muller Glia Cells, while rods only get the recycled 11-cis retinal from the RPE cells. **HAVING TROUBLE BATTING IN CRICKET AND TEMPORARY BLINDNESS WHEN LEAVING A CINEMA:** **= Bradyopsia** Bradyopsia is known as 'slow vision', \> caused by mutations in the RGS91 or R9AP genes, *which results in difficulty adapting to sudden changes in bright light and difficulty in seeing moving objects at low contrast.* - *[RGS91] (expressed in Retina)/R9AP (expressed in brain) are genes involved in the recovery of photoreceptors after light exposure.* - Interestingly, people with this mutation have better/faster night vision as people with no RGS91, PDE is more at low light levels -\> shorter turnover of cGMP -\> cGMP channels remain open at low light. -  *\ * **[LECTURE 7 -- WEEK 3 -- WHY DO WE NEED VISUAL ADAPTATIAN? ]** **Lecture concept:** *Our vision depends on our ability to detect small differences or changes in:* **What is the RPE?** - **Location**: The RPE is a single layer of pigmented cells that lies between the photoreceptors (rods and cones) of the retina and the choroid, which is the vascular layer of the eye that supplies blood to the retina. - **Pigmentation**: The cells of the RPE are heavily pigmented with melanin, which gives them a dark appearance. This pigmentation helps to absorb excess light, preventing it from scattering within the eye and thus improving visual acuity - **Further functions;** Absorption of light (heat); barrier function; transport of nutrients, ions and water; phagocytosis of shed OS; Photopigment recycling (all-trans-retinal to 11-cis-retinal) **Autosomal recessive:** Where a parent who has one faulty gene copy and one normal gene copy, is a carrier and does not usually have symptoms. - ***ARIRD = Autosomal Recessive Inherited Retinal Dystrophy*** - For a child to be affected, both parents would need to be carriers of a gene variant I the same gene. If both parents are carriers, child can be: - 25% chance affected - 25% chance unaffected and not a carrier - 50% chance will be an unaffected carrier. **EXAMPLE 1 of *ARIRD:*** - **[ABCA*4*-related IRDs]** - ATP-binding cassette transporter 4 - **Involved in the recycling of 11-cis retinal into all-trans retinal** - sits in the rim of the outer segment of the photoreceptor - Does so by flipping *N-retinylidene phosophatidylethanolamine (NrPE)* in photoreceptor disc membrane and prevents build up of vitamin A derivatives, which are toxic to the RPE - **Has 50 exons:** An exon is a segment of a gene that codes for proteins. In the process of gene expression, the DNA sequence of a gene is transcribed into messenger RNA (mRNA). This mRNA transcript contains both exons and introns (non-coding regions). During a process called splicing, introns are removed, and the exons are joined together to form the final mRNA sequence that is translated into a protein. **[ABCA*4*-related IRDs]** \> can cause **Stargardt disease** (muscle atrophy), retinitis pigmentosa (form of cone dystrophy), and cone-rod dystrophy. - When ABCA4 is not present, it results in a build-up of vitamin A, which is where **RPE breaks down** (pigment epithelium cells in between the photoreceptors of retina and the choroid. **Autosomal Dominannt:** Where the phenotype trait it seen in those with one copy of the variant. - **50% chance of affected person to pass faulty gene onto child** **Mechanism of disease:** 1. **Loss of function** -- one copy of gene active means it is not enough to maintain normal function 2. **Dominant negative** & **gain-of-function --** if one gene is defective and other is not, the defective gene can still impede the normality function of the normal gene. - **Rho-related retinitis pigmentosa (rod-cone dystrophy)** - Rho encodes for rhodopsin - 20-30% of AD rod-cone dystrophies - AD inherited retinal diseases less frequent than autosomal recessive (AR) diseases -- also less severe than AR and X-linked. **X-Linked: Faulty gene on the X chromosome** - Female with faulty x chromosome usually do not show symptoms (x-inactivation) - Males will, as they only have 1 x X-chrome - No male to male transmission **If mother is carrier but father is healthy:** - Each son has 50% chance of being affected - Each daughter has 50% chance of being a carrier lie mother. - **Retinitis X-linked-pigmentosa GTPase regulator** - Found in photoreceptor outer segments - Essential for the maintenance of photoreceptor viability **Mitochondrial inheritance:** - Mitochondria have their own DNA -- 37 genes - Mutations in mitochondrial genes passed on through the mother (maternal inheritance) - Both males and females can be affected **[LECTURE 8 -- WEEK 3 -- THE BIONIC EYE]** **Lecture concept:** *[THE BIONIC EYE]* **OPTOGENETICS -- gene therapy** - **In RPE** photoreceptors are degenerated (die), but the other retina cells are intact, and so one could innervate them to **make them light responsive.** - **One takes a light sensitive protein from an algae,** and then takes the gene and inserts it into the DNA of specific neurons in the brain, to allow for bipolar and ganglion cells to become light responsive themselves. **The protein from the algae, is [an ion channel] that opens in response to blue light and allows for depolarisation.** - **What does this mean?** =\> This means that you can cause neurons to fire just by flashing **blue light!!** **\ ** **[LECTURE 9 -- WEEK 4 -- NON-INVASSIVE ASSESSMENT OF THE EYE]** **Lecture concept:** *[NON-INVASIVE ASSESSMENT OF THE EYE ]* **Binocular vision =** Sharing of visual pathways from both eyes in separate hemispheres (left side of each eye is processed on the right hemisphere & right side of each eye is processed on the left hemisphere) *This gives us the ability to locate things in space much better.*  **[SUMMARY OF OCULAR ELECTODIAGNOSTICS -- FOR EXAM!]**  **\*HAND HELD ERG -- Can be used to detect seizures and genetic predisposition to seizures in children\*** **[LECTURE 10 -- WEEK 4 -- VIRAL VECTORS & RETINAL GENE THERAPY]** **Lecture concept:** *[What is **gene therapy**, and what can it do? ]* **Gene therapy:** ***Experimental technique that uses genes to treat or prevent disease. Can be used for:*** - ***Replace mutate disease-causing gene*** - ***Gene inactivation*** - ***Introduce a new gene to help fight disease*** - ***Generate secreted proteins*** **EX VIVO =\>** Gene therapy where targeted cells are removed from body, altered, and then transplanting them back not patient. **IN VIVO =\>** Gene therapy where direct systemic administration (intravenous) to the patient wherein the targeted cells remain the body. **\[CURRENT CHALLENGES FOR OCULAR THERAPY\]** - Introducing the right level of AAV into the body - Correct timing for introducing AAV - Specificity and efficacy of current vectors - Delivery: Subretinal vs Intravitreal - Pre-existing immunity (PEI) and acquired immunity - Large genes - Clinical outcome measures 1. LEVELS: - **Hard to assess how much of defective/missing protein we need in humans, but, visual rescue of animal models of retinal degeneration with mutations in high expressing genes is possible.** *How could we improve this?* - Better vector design (promotor, improved AAV capsids, gene sequencing optimization - Clinical trials comparisons - **PDE6B gene therapy (***treated mice at 9 days of age, able to recover most of eye cells like rods and ganglion cells, where an increase in the **PDE6B gene** allowed for retinal recovering) -- Same thing was done in the rods of dogs.* 2. **TIMING: Window for treatment** Natural history of disease - Onset - Progression - Mutation-specific effects - Inter-individual differences - Effect of environmental factors. - **CNGB3 gene therapy (***treatment for cones with **CNGB3 gene --** complete loss of colour vision which is rescued by introducing greater **CNGB3 proteins) --** mice that were treated at day 30, recovered colour vision as well as the regular wild-type mice's vision -- while when treated at day 150, the recovery was only minimal and not a normal physiological colour vision)* - **Achromatopsia:** Rare genetic disorder that results in the complete or partial loss of colour vision. 3. **SPECIFICITY & EFFICACY OF CURRENT VECTORS:** Development of better vectors / AAV biology - *Alternative serotypes / species* - *Physico-chemical modification* - *Capsid engineering (mutagenesis; rational design; directed evolution; in silico design)* **[LECTURE 11 -- WEEK 4 -- RETINAL MOSAIC & SAMPLING]** **Lecture concept:** *[How does the retina **sample** visual space, and how does this relate to the anatomical structure of photoreceptors & ganglion cells?]* - *Smallest population of S-cones (only 10% of all cones in retina, the rest is M & L)* - **Spatial resolving capacity** of retina / visual system will be related to photoreceptor spacing. - **Resolution** limit is approx. 40 to 60 cycles / degree. - At **30 cycles/degree** vision is at **'20/20'** which means great resolving capacity and visual acuity, at **3 cycles/degree** vision is at **'20/200'** which means much lower resolving capacity. **\ ** **Retinal Periphery \>** beyond 5 eccentricity, suggests there to be a resolution limit in retinal periphery set by neuronal factors (retina/brain). **RGCs pool signal** from multiple photoreceptors in retinal periphery -- should set resolution limit, therefore, the **GCs instead of photoreceptors** in the periphery specifically that are the limiting factor of our spatial resolution. Between the photoreceptors and the GCs, where there is the **lowest density** correlates to the factor which is impeding spatial resolution. **However,** it is actually the midget-GCs (parvocellular) which limit our vision (80-90% of RGCs) - Smaller dendritic fields - Smaller centre-surround receptor feilds - Complete coverage of all eccentricities 'In the context of vision, **aliasing** refers to the distortion or misrepresentation of visual information due to limitations in the spatial resolution of the visual system. It occurs when the frequency or detail of visual stimuli exceeds the resolving capacity of the eye or visual system, leading to artifacts or misleading perceptions.' **Aliasing --** - Results from inadequate sampling of continuous function (e.g under sampling) - Signal reconstructed from samples differs from original, continuous signal - Alias typically has lower spatial frequency & different (i.e. non-veridical) orientation. A close-up of a document Description automatically generated **So, you will get weird tiger-stripe like vision when the spatial frequency is too high to be able to resolve, so a spatial frequency that is ABOVE THE NYQUIST LIMIT. Samling frequency must be at least twice the highest spatial frequency to adequately represent signal.** - in central fovea, L- & M- cone density high enough to capture all the information that survives the blurring by eye\'s optics - blurring by eye\'s optics helps prevent aliasing - in retinal periphery (lower cone density), effect of aliasing reduced by the disarray in sampling mosaic = produces noisy pattern rather than plausible object - aliasing (and other) studies have revealed an S-cone spacing of 10 minutes of arc, and L- & M-cone spacing of 30 seconds of arc ***WHY ARE S-CONES SO SPARSE IN COMPARISON TO M/L CONES?*** - Chromatic aberration in eye blurs short-wavelength image - Sparse sampling is adequate to capture retinal image seen by S-cone mosaic - Blue bends better (refracts better) -- eyes are a little bit short sighted for blue light (little bit out of focus on the retina), always produces 'fuzzy' image, so why would the eye want more of them (s-cones)?? That's the logic \^. ***\ *** **[LECTURE 12-- WEEK 5 -- IMAGING RETINAL CELLS]** **Lecture concept:** *[How do we take images of the retina and what does this show us? ]*