hello and welcome to Insight oftalmology this is Dr Amrit welcoming you to another lecture today we are studying photo transduction or the visual cycle first is what is photo transduction light falls on retina and it is absorbed by the photosensitive pigments which are present in the rods and cones this will cause a series of photochemical changes in the rods and Cone finally leading to the electrical changes in their membrane potential and this process of changing of light energy into electrical changes finally leading to vision is called photo transduction we know that the rods and the cones they basically have the outer segment an inner segment and a synaptic region now the question is where does photo transduction occur it basically occurs in the discs which are present in the outer segment of the rods and also in the cones we know the outer segment of Rod actually have this arrangement of several discs stacked on each other now now if we actually Zoom this dis of the outer segment let me now introduce to you the various characters of this video in this video we shall be studying about the ropin and how ropin affects another character that is the transducin and we have the phosphor Diest which is affected by the transducin however you should know that phosphor Diest always exist with its two gamma subunits apart from that we shall be talking about another important character and that is the sodium channels so first of all what is ropson ropin is actually a photosensitive visual pigment which is present in the disk of the outer segments of the rod it is actually a g protein coupled receptor it is one of those Serpentine receptors it has two subunits the one basic one is a protein and apart from the protein which is called opsin we have a carotenoid this carotenoid is derived from vitamin A and therefore it is also called vitamin a alide or also called retinene apart from that the name with which it is famous is the 11 Cy retinol so here you can see in Orange is the option and we have a small component of the vitamin A which is the 11 CIS retina very important component now going a step further so let us see what exactly happens when light strikes the retina inside the ropson molecule where we have the 11 Cy retina at the carbon 11 and carbon 12 Bond there will be a confirmational change such that we get from 11 C retinol all trans retinol so these two are actually isomers that means the 11 C retinol and the all trans retinol if you carefully observe they have similar chemical composition that mean the same number of carbon atoms the same number of hydrogen atoms however their shapes are different so ropson will be actually converted that means the 11 CIS retinol in the the adoption will finally be converted into the all trans retinal through a series of steps so the steps are as follows the ropin is first converted into the Bor ropin then we get Lumi ropin then we get meta ropin one and finally we get meta ropin 2 which is the active ropin containing the all trans retinol remember all this happens in the presence of light so as I told you that activated ropin and how was the rops in activated by the presence of life it basically has all trans retinol in it now as the confirmational change occurs and it becomes metod opsin to they cannot live together opsin and all trans retinal will now have to separate from each other and this process which is induced by light that is the separation of the opsin from the ultan retinal is called ropson bleaching or the photo decomposition are you with me so we completed the character adoption next we have the transducer okay this guy in red color so basically our activated ropin has the all trans retina right now this is called active ropin because it is going to go and activate our next protein that is the transducin so our next character that is a transducin is a GDP GTP exchange proteins now it has two forms it has an inactive form and an active form the active form basically has the GTP attached to it and the inactive form has a GDP attached to it the question is how will it be activated so it is our activated opsin which will go and bind to transducin and activate the transducin so our activated opsin molecule we know how it gets activated from the dosin to metaoption 2 metop adoption 2 actually has all trans retinol the option will now separate from the all trans retinal and this option will now develop this binding site on it and now what happens is that with this binding site this option is going to go and bind to your inactive transduc which had GDP before and that GDP will now be exchanged with GTP and therefore we will get an active transducin now once we have an active ropion an active transducin let us now introduce the Third character and that is the phosphor diestra enzyme so our phosphor diestra enzyme is also present in the membrane and the thing is that in its inactive form it has these two gamma units attached on the either side and obviously once you remove these gamma units from the phosphor diestra you will have an active molecule of phosphor diestra enzyme again the question is what will activate phosphor diast so you might have guessed it by now it is our activated transducin which has a GTP in it so that will come and activate your inactive phosphor diestra okay so what happens is it basically your transducin is actually a trimeric protein that means it has three parts so one part of your transducin which has GTP attached to it is going to come down to your gamma unit of the phosphor destr and it will actually attach to the gamma unit of the phospho diay and subsequently it will try to separate that gamma unit from your phosphor diestra gamma complex but the thing is we still have this phosphor diestra as inactive because of the presence of one more gamma unit to it so what will happen next one more transducin which is activated by your opsin will come forth and try to remove this gamma unit and therefore finally the gamma units from both the sides of the phosphor dry stay will be removed and you will will get an activated phosphor diestra so now we got our activated phosphor diestra molecule but did I tell you what is the function of this phosphor Diest the function is that it will convert your cyclic GMP to the normal gine mono phosphate or the GMP so the cyclic GMP will represent in brown color and the GMP will represent in the blue color now what happens is as you can see as your phosphor G will get activated all your cyclic GMP is getting converted to your GMP so obviously the cyclic GMP concentration is coming down and there will be a decrease in the level of cyclic GMP so remember that cyclic GMP is also very important component and you will understand it better when I introduce to you the next character of the story which is the sodium channels your sodium channels can either be opened or it could be closed so the the top one is a open sodium Channel and the bottom one is a closed sodium Channel now if you see carefully I have drawn a brown color ball near the open sodium Channel and that brown color is nothing but it is a cyclic GMP whereas the blue color is a normal GMP so you can say that the sodium channels will open in the presence of your cyclic GMP and they will close Whenever there is a normal GMP around that channel so basically in dark what happens is these channels will be open and therefore the sodium channels will be open in dark because of the increased level of cyclic GMP however in the presence of light do you remember all the characters what was happening light was bringing all those characters and activating them whether it was ropin transducin and then the phosphor diestra enzyme so this phosphor di enzyme then led to decrease in the cyclic GMP concentration and ultimately what will happen as the cyclic GMP goes down the GMP increases and therefore the channels will remain closed and therefore in light the channels will actually close so that's very important Point regarding this character so basically what is happening in our dark is that we have cyclic GMP we have open sodium channels and because of the increased level of cyclic GMP more and more amount of sodiums is actually entering the cell the cell is becoming relatively positive and this is called deol ization which occurs in the dark phase whereas in light what happens we have our active character of phosphor diestra which is actually converting your cyclic GMP to your GMP and the GMP concentration is rising and therefore the channels are closed and therefore the sodium is going to start accumulating outside the cell the inside of the cell is going to become more and more negative and this is called hyperpolarization which occurs in the light phase so do you know that some changes also occur in the inner segment of the rod so in the inner segment of the rod we have a sodium pump which will actively keep on pumping the sodium out so obviously the inside of the cell in the inner segment will become negative because all the positives are coming out and obviously in the outer segment we know we have seen that the sodium from outside is entering inside through those sodium channels right this is what we already saw and these channels are going to open induct so because of this variable ionic conduction inside the cell that means the outer segment is relatively positive in the dark because of the sodium entering and the inner segment is relatively negative because the sodium is exiting through the pump we get a particular type of current flowing from the outer segment inner segment and going up to your CTIC Terminals and this current is called the dark current okay and this dark current is basically basically because of the depolarization of the photo receptor I already told you what is depolarization as the receptor gets depolarized we will have the release of the neurotransmitter from the synaptic Terminals and mostly this neurotransmitter is glutamate there are some changes between other sensory cells and the rods and cones in the other sensory cell the receptor will get activated by depolarization and then we will have an action potential generation and finally we will have the release of the neurotransmitter however in rods and cones you saw that in dark the receptor was depolarized however when light came about there was actually receptor hyperpolarization and then that leads to generation of graded change in the potential and not action potential moreover the neurotransmitter was being released in the dark and let me tell you it is also released in the light also however there's a graded change in the amount of neurotransmitter that is being released at the post synaptic neurons so that is some important differences between the sensory cells and the rods and cones so basically what happens in dark there is some amount of negativity inside that is called the resting membrane potential and that is about 40 molts and obviously when light strikes there is a progressive increase in the negativity inside and you will see the the membrane potential reaching minus 65 m volts because of the hyperpolarization so this over here is actually an introduction to another character of the story and that is the calcium channels okay understanding this character is very important if you want to understand how this entire process of photor transduction will actually come to a halt okay so the volted Gated calcium channels are actually present at the preoptic terminals okay so you can see that here I've drawn them in pink color the these recycles are actually containing your neurotransmitters now I already told you that in the outer segment in the dark what is happening the sodium channels are open and the sodium is entering the outer segment now let me tell you that along with sodium a little bit amount of calcium is also going to enter into the outer segment to keep the photo receptors depolarized because the amount of calcium in the rods is more IND dark the number of calcium channels in the synaptic terminal will also be more will be open more and this will lead to more amount of neurotransmitter release so the rate of neurotransmitter release is correspondingly great in compared to dark compared to light so in the light what happens again we know that in light what happens the sodium channels will close so even the calcium enters to the sodium channels the amount of calcium will also be less the rods are hyperpolarized the number of open calcium channels will therefore be reduced and the rate of neurotransmitter will also be reduced at the synaptic terminal so in dark we have depolarization that ultimately causes an increased neurotransmitter release however in light we have hyperpolarization and that causes a decreased neurotransmitter release okay so this is what you can actually understand here through this diagram so in the dark what is happening the sodium is able to enter even the calcium is able to enter the cyc GMP level AB are more and what do we see we see that the this arrow is actually towards the de rise take that means the inside of the cell is not as negative as compared to the light so in light what happens the cyclic GMP levels will be less the uh GMP levels will be more and therefore the sodium channels will be closed the inside of the cell will become more negative see the arrow is tilting more towards the negative side and there will be hyperpolarization therefore in the presence of Darkness there is depolarization and in light there is hyperpolarization of the receptor now I think this would be a right time to introduce you to the signal amplification concept we know that in the disc segment or in the dis of the outer segment we have these various discs and all these dis individually also have so many molecules of transducin sitting on that a single light activated adoption can actually activate about 800 transducin molecules which is about 8% of the total molecules which are sitting on the disk surface so just look at that number now either one or two translucent molecules will go and activate one phosphor Diest molecule okay now actually there's a controversy about it that some sources say that we need two translucent molecules to activate one phosphor di enzyme and some sources say that we need only one translucent molecule to activate one phosphor di molecule okay so what do you think about it just let me know in the comment section now each phosphor Diest can actually break down about six cyclic GMP molecules okay so this there's so much amount of signal amplification that a single Photon by a ropson molecule can actually lead to closure of about 200 sodium ion channels and that is about 2% of the number of channels in each Rod that are actually open in the duck right and this this amount of Channel closure will cause a net change in the membrane potential of about 1 million volt okay so this light amplification the magnitude of this amplification actually varies with the prevailing level of Illumination you change the level of Illumination and you can change the amplification signal now this is called light adaptation so the concentration of calcium in the outer segment is very very important the cyclic GMP gated channels in the outer segment as I told you they are permeable to both sodium as well as calcium and therefore when the light causes closure of these Channel there will be a net decrease in the internal calcium concentration as well now as the internal calcium concentration goes down what happens is that there's another protein which gets activated another enzyme gets activated and that enzyme is the galate cycles and it will now leads to production of the cyclic GMP and we know what happens when the cyclic GMP increases so when the cyclic GMP will increase the sodium channels will now open apart from that the cyclic GM this Guan Cycles will also increase the Affinity of the cyclic GMP gated channels for the cgmp this will cause the sodium channels to open and sodium and calcium will now enter the cells the calcium concentration will now increase and the photo ructions U amplification whatever we saw will now start decreasing okay so that is how the photot transduction is actually control okay now there's another protein which is called arrestin so this arrestin basic basically what what it does is that it actually blocks the ability of ropin to activate transducin and facilitates the breakdown of activated adoption so this arrestin is going to arrest the adoption and prevent this red option for further activating transducin so definitely photot transduction is an important process but everything needs to be controlled after some time and we have this important calcium channels we have this gal cyclist that we studied about and also we have this important protein molecule which is called a Restin which will regulate our photo transduction so after this photo transduction stops the red option will undergo regeneration which is nothing but the all trans retinol will be converted to 11 set retinol again which is called which is done by the retinal isomerase enzyme the 11 say retinal will again join with opsin and leads to formation of R opsin this occur in the retinal Pig pment epithelium by the way so now let us join all these dots together so there are basically three main photochemical reactions which are occurring in the rods we have a rops and bleaching rops and regeneration and the visual cycle now it'll become very easy for you the first step is redops and bleaching we saw that when light strikes the retina the 11 C retinol will undergo isomerization change and gets converted into Old trans retinol to a series of changes of course now this process is called ropion bleaching or photo decompression the next step is the redops and regeneration we know how it occurs all trans retinal gets converted back to its original form ropson which was broken down again forms a new ropson this is called ropson regeneration so degeneration basically is dependent on light however the Regeneration occurs equally in light as well as dark that's important point so the first process by which 11 says retinol is converted into all trans retinol is called photo bleaching or photo decomposition and the second process by which it is regenerated back to 11 say retinol is called photo regeneration and there is always a balance in the eye between the two now this balance and this cycle is called the vault's visual cycle so that was a detailed video on photo transduction I hope you were able to follow it I hope it was useful thank you and have a nice day [Music] yeah