ERGs PART 3 Sylvain Bolay Novembre 16, 2010 Tuesday, November 16, 2010

Transcription

1 ERGs PART 3 Sylvin Boly Novemre 16, 2010

2 Historil view 1865: The first eletroretinogrm is reorded y Alrik Frithiof Holmgren. The omponents of the retinl tion potentil in mmmls nd their reltion to the dishrge in the opti nerve. Grnit R. ; J Physiol Fe 8;77(3): : The eletril response of the eye to light flsh ws first desried s omposed of two wves. [The time reltions of the photo-eletri hnges in the eyell of the frog / Goth F. / J Physiol Jun 15;29(4-5): ] First: the orne eme negtive. Then: positive wve of lrger mplitude ppered Then it ws desried s eing omposed of three wves. [The form nd mgnitude of the eletri response of the eye to stimultion y light t vrious intensities / W. Einthoven nd W. A. Jolly / Jnury 1, 1908 Experimentl Physiology, 1, ] First: ornel negtive wve ppers immeditely fter turning on light stimulus. Seond: positive wve. Third: slower positive wve. These uthors work ws the foundtion for the form of nlysis of the ERG used to present dy. The wves re lled -, - nd -wves. An dditionl ornel-positive wve, tht is more rrely reorded t the end of the stimulus, is lled the d-wve. They suggest tht the wves reflet trnsient hemil proesses.

3 The first eletroretinogrm is reorded y Alrik Frithiof Holmgren. The omponents of the retinl tion potentil in mmmls nd their reltion to the dishrge in the opti nerve. Grnit R. ; J Physiol Fe 8;77(3): : The eletril response of the eye to light flsh ws first desried s omposed of two wves. Historil view [The time reltions of the photo-eletri hnges in the eyell of the frog / Goth F. / J Physiol Jun 15;29(4-5): ] First: the orne eme negtive. Then: positive wve of lrger mplitude ppered Then it ws desried s eing omposed of three wves. [The form nd mgnitude of the eletri response of the eye to stimultion y light t vrious intensities / W. Einthoven nd W. A. Jolly / Jnury 1, 1908 Experimentl Physiology, 1, ] First: ornel negtive wve ppers immeditely fter turning on light stimulus. Seond: positive wve. Third: slower positive wve. These uthors work ws the foundtion for the form of nlysis of the ERG used to present dy. The wves re lled -, - nd -wves. An dditionl ornel-positive wve, tht is more rrely reorded t the end of the stimulus, is lled the d-wve. They suggest tht the wves reflet trnsient hemil proesses.

4 Historil view

5 Responses to right light stimuli pplied in the drk-dpted stte. ERG signl eliited y 900ms step of light. Shows n wve nd wve omplex seprted from the d wve whih is generted t the stimulus flling edge.

6 Responses to right light stimuli pplied in the drk-dpted stte. ERG signl eliited y 900ms step of light. Shows n wve nd wve omplex seprted from the d wve whih is generted t the stimulus flling edge.

7 Responses to right light stimuli pplied in the drk-dpted stte. Tod / Bullfrog Bright light stimulus of 40s. The wve nd wve re followed y the slow ornel positive wve. At the stimultion flling edge, d wve develops.

8 Responses to right light stimuli pplied in the drk-dpted stte. Tod / Bullfrog Bright light stimulus of 40s. The wve nd wve re followed y the slow ornel positive wve. At the stimultion flling edge, d wve develops.

9 Responses to right light stimuli pplied in the drk-dpted stte. Fst 20ms right flsh (Therefore) Only the wve nd wve re seen

10 Responses to right light stimuli pplied in the drk-dpted stte. Fst 20ms right flsh (Therefore) Only the wve nd wve re seen

11 Responses to right light stimuli pplied in the drk-dpted stte. Fst 20ms right flsh (Therefore) Only the wve nd wve re seen. Fst osilltions n lso e seen on the rising edge of the wve.

12 Responses to right light stimuli pplied in the drk-dpted stte. Fst 20ms right flsh (Therefore) Only the wve nd wve re seen. Fst osilltions n lso e seen on the rising edge of the wve.

13 Responses to right light stimuli pplied in the drk-dpted stte. T k e - H o m e M e s s g e These ERGs, in the different speies, lerly differ in mplitude nd pttern. Some of this vriility is due to speies differenes, prtiulrly, the reltive densities of rods nd ones. The reorded wveform is ffeted y tehnil ftors suh s: durtion nd intensity of photo-stimultion method of reording. Nevertheless, ERG responses of turtle, ullfrog, rit nd humn, in ddition to those reorded from other verterte speies, re hrterized y the si fetures of negtive wve followed y positive wve.

14 Historil view 1911: The ERG is divided into 3 omponents: I, II nd III.. [Üer die Netzhutströme / Piper, H. / Arhiv für Physiologie, 1911 no. 1/2: ][Reltions etween the mplitudes of spontneous sdes nd visul responses / John C. Armington nd Mrie B. Bloom / J Opt So Am Sep;64(9): ] The intertion etween the first two wves I nd II results in the formtion of the nd wves. Wve III is equivlent to the -wve. 1933: ERG reordings from nesthetized t using ornel eletrodes. [ The omponents of the retinl tion potentil in mmmls nd their reltion to the dishrge in the opti nerve. / Grnit R. / J Physiol Fe 8;77(3): ] Grnit oserved the grdul removl of the different omponents s the level of nesthesi ws deepened (ether nrosis). He termed the different omponents in sequene of their dispperne: P I, P II nd P III. The P I omponent is slow orne-positive wve. P II is lso ornel-positive wve tht rises reltively fst to pek mplitude nd then reovers to n intermedite potentil while the light stimulus is still on. P III (the most resistnt to the level of nesthesi) is orne-negtive wve tht develops fster thn the other two nd remins s negtive potentil for s long s the light stimulus is on.

15 1911: The ERG is divided into 3 omponents: I, II nd III.. [Üer die Netzhutströme / Piper, H. / Arhiv für Physiologie, 1911 no. 1/2: ][Reltions etween the mplitudes of spontneous sdes nd visul responses / John C. Armington nd Mrie B. Bloom / J Opt So Am Sep;64(9): ] Historil view The intertion etween the first two wves I nd II results in the formtion of the nd wves. Wve III is equivlent to the -wve. 1933: ERG reordings from nesthetized t using ornel eletrodes. [ The omponents of the retinl tion potentil in mmmls nd their reltion to the dishrge in the opti nerve. / Grnit R. / J Physiol Fe 8;77(3): ] Grnit oserved the grdul removl of the different omponents s the level of nesthesi ws deepened (ether nrosis). He termed the different omponents in sequene of their dispperne: P I, P II nd P III. The P I omponent is slow orne-positive wve. P II is lso ornel-positive wve tht rises reltively fst to pek mplitude nd then reovers to n intermedite potentil while the light stimulus is still on. P III (the most resistnt to the level of nesthesi) is orne-negtive wve tht develops fster thn the other two nd remins s negtive potentil for s long s the light stimulus is on.

16 Historil view

17 P-I, P-II, P-III to,

18 P-I, P-II, P-III to, In summry, we see tht the negtive wve is the flling edge of the negtive P III omponent; the positive wve reflets the summtion of P II nd P III while the slow wve follows P I whih is offset y the summtion of P II nd P III.

19 The origin of the mjor ERG wves. The -wve The wve is known to originte in the pigment epithelium [ The origin of the eletroretinogrm. / Noell WK / Am J Ophthlmol Jul;38(1:2):78-90.]. This interprettion of the wve origin ws proven diretly when intrellulr reordings were mde from pigment epithelil ells [ Intrellulr responses to light from t pigment epithelium: origin of the eletroretinogrm -wve / Steinerg RH, Shmidt R, Brown KT / Nture Aug 15;227(5259): ]. The potentil hnges tht were reorded from these ells in response to light stimuli were identil in shpe nd temporl properties to the ERG wve. When the retin ws seprted from the, the ERG response ontined norml nd wve, ut wve disppered. Choroidl lyer ERG reording from the skte eyeup, Peppererg et l., 1978

20 The origin of the mjor ERG wves. The -wve The wve is known to originte in the pigment epithelium [ The origin of the eletroretinogrm. / Noell WK / Am J Ophthlmol Jul;38(1:2):78-90.]. This interprettion of the wve origin ws proven diretly when intrellulr reordings were mde from pigment epithelil ells [ Intrellulr responses to light from t pigment epithelium: origin of the eletroretinogrm -wve / Steinerg RH, Shmidt R, Brown KT / Nture Aug 15;227(5259): ]. The potentil hnges tht were reorded from these ells in response to light stimuli were identil in shpe nd temporl properties to the ERG wve. When the retin ws seprted from the, the ERG response ontined norml nd wve, ut wve disppered. Choroidl lyer ERG reording from the skte eyeup, Peppererg et l., 1978

21 The origin of the mjor ERG wves. The -wve The pigment epithelium ells re funtionlly symmetril ells with their sl memrne (towrd the horoid) less permele to potssium ions thn the pil memrne (retinl side). This symmetry uses onstnt potentil differene etween the retin nd the horoid with the retinl side positive reltive to the horoidl side (The stnding potentil of the eye). Choroidl lyer in the drk: Vp > V I s pil men V p -85 ± 7mV n =18 ells + + R p V' p V' R s (shunt) men TEP 19 ± 6mV n = 66 ourtesy Willim S. Strk ( sl Adpted from Clrk, 1986 men V -69 ± 8mV n = 18 ells R I s Griff et l., 1984

22 The origin of the mjor ERG wves. The -wve Choroidl lyer pil + men TEP 19 ± 6mV n = 66 sl Adpted from Clrk, 1986

23 The origin of the mjor ERG wves. The -wve Mesurements with potssium-sensitive miroeletrode in the photoreeptor lyer shows light-indued derese in the extrellulr onentrtion of potssium ions, due to lightindued eletril tivity in the photoreeptors. The redution in the extrellulr onentrtion of potssium ions ner the pil memrne of the pigment epithelil ells is expressed s n inrese in the trns-epithelil potentil with the retinl side eoming more positive reltive to the horoidl side. This is the ERG -wve when reorded with ornel eletrode (Okley nd Green, 1976; Okley, 1977) Choroidl lyer pil + men TEP 19 ± 6mV n = 66 sl Adpted from Clrk, 1986 To simplify the omprison, the KRG responses re inverted, thus positive defletion in this figure mens redution in extrellulr onentrtion of potssium ions.

24 The origin of the mjor ERG wves. The -wve T k e - H o m e M e s s g e Although the -wve origintes from the pigment epithelium, it depends upon the integrity of the photoreeptors, euse light sorption in the photoreeptors triggers the hin of events leding to the derese in extrellulr onentrtion of potssium ions. Therefore, the ERG -wve n e used to ssess the funtionl integrity of the photoreeptors, the pigment epithelil ells nd the intertions etween them. Choroidl lyer

25 The origin of the mjor ERG wves. The -wve The ERG -wve is the leding prt of Grnit's P-III omponent. The most importnt informtion on the origin of these wves ws otined from ERG reordings with intr-retinl miroeletrodes (Tomit, 1950; Brown nd Wiesel, 1961, 1961; Brown nd Murkmi, 1964; Brown, 1968). These studies suggested the photoreeptor lyer s the origin of the fst P-III wve. Differentil reording in the rt retin using two miroeletrodes reveled tht the -wve resulted from extrellulr rdil urrent. Choroidl lyer GMP-gted tioni hnnel 80% N % C % Exhnger C 2+ ; N + C 2+ Memrne C 2+ N + C 2+ N + C 2+ N + N + photoreeptor C 2+ N + C 2+ N + C 2+ C 2+ C 2+ N + N + N +

26 The origin of the mjor ERG wves. The -wve The ERG -wve is the leding prt of Grnit's P-III omponent. The most importnt informtion on the origin of these wves ws otined from ERG reordings with intr-retinl miroeletrodes (Tomit, 1950; Brown nd Wiesel, 1961, 1961; Brown nd Murkmi, 1964; Brown, 1968). These studies suggested the photoreeptor lyer s the origin of the fst P-III wve. Differentil reording in the rt retin using two miroeletrodes reveled tht the -wve resulted from extrellulr rdil urrent. Choroidl lyer GMP-gted tioni hnnel 80% N % C % Exhnger C 2+ ; N + C 2+ Memrne C 2+ N + C 2+ N + C 2+ N + N + photoreeptor C 2+ N + C 2+ N + C 2+ C 2+ C 2+ N + N + N +

27 The origin of the mjor ERG wves. The -wve The ERG -wve is the leding prt of Grnit's P-III omponent. The most importnt informtion on the origin of these wves ws otined from ERG reordings with intr-retinl miroeletrodes (Tomit, 1950; Brown nd Wiesel, 1961, 1961; Brown nd Murkmi, 1964; Brown, 1968). These studies suggested the photoreeptor lyer s the origin of the fst P-III wve. Differentil reording in the rt retin using two miroeletrodes reveled tht the -wve resulted from extrellulr rdil urrent. Choroidl lyer GMP-gted tioni hnnel 80% N % C % Exhnger C 2+ ; N + C 2+ Memrne C 2+ N + C 2+ N + C 2+ N + N + photoreeptor C 2+ N + C 2+ N + C 2+ C 2+ C 2+ N + N + N +

28 The origin of the mjor ERG wves. The -wve The ERG -wve is the leding prt of Grnit's P-III omponent. The most importnt informtion on the origin of these wves ws otined from ERG reordings with intr-retinl miroeletrodes (Tomit, 1950; Brown nd Wiesel, 1961, 1961; Brown nd Murkmi, 1964; Brown, 1968). These studies suggested the photoreeptor lyer s the origin of the fst P-III wve. Differentil reording in the rt retin using two miroeletrodes reveled tht the -wve resulted from extrellulr rdil urrent. This is the 'light' urrent nd silly reflets the redution in the 'drk' urrents due to light sorption in the photoreeptor outer segments, nd losure of GMP-gted tioni hnnels (Penn nd Hgins, 1969; Sillmn et l., 1969). Choroidl lyer GMP-gted tioni hnnel 80% N % C % Exhnger C 2+ ; N + C 2+ Memrne C 2+ N + C 2+ N + C 2+ N + N + photoreeptor C 2+ N + C 2+ N + C 2+ C 2+ C 2+ N + N + N +

29 The origin of the mjor ERG wves. The -wve The ERG -wve is the leding prt of Grnit's P-III omponent. The most importnt informtion on the origin of these wves ws otined from ERG reordings with intr-retinl miroeletrodes (Tomit, 1950; Brown nd Wiesel, 1961, 1961; Brown nd Murkmi, 1964; Brown, 1968). These studies suggested the photoreeptor lyer s the origin of the fst P-III wve. Differentil reording in the rt retin using two miroeletrodes reveled tht the -wve resulted from extrellulr rdil urrent. This is the 'light' urrent nd silly reflets the redution in the 'drk' urrents due to light sorption in the photoreeptor outer segments, nd losure of GMP-gted tioni hnnels (Penn nd Hgins, 1969; Sillmn et l., 1969). It hs now een shown tht P-III n e divided into further two omponents (Murkmi nd Kneko, 1966; Sillmn et l., 1969): fst P-III nd slow P-III Choroidl lyer Fst P-III Slow P-III The slow omponent of the P-III nnot e identified in regulr ERG response due to the lrge mplitude positive P-I wve.

30 The origin of the mjor ERG wves. The -wve By seprting the retin from the pigment epithelium, P-I n e eliminted. By exposing the retin to drugs, suh s sprti id, tht lok synpti trnsmission from the photoreeptors to the neurons in the inner nuler lyer, P-II n e eliminted. Thus the P-III omponent n e isolted nd studied (Witkovsky et l., 1975). Choroidl lyer

31 The origin of the mjor ERG wves. The -wve... nd more Mesurements of the extrellulr onentrtion of potssium ions nd of the isolted P-III omponent of the ERG t different retinl depths revel the involvement of retinl glil (Müller) ells in the genertion of the slow P-III. The Müller ells re highly permele to potssium ions. Therefore, the redution in the extrellulr onentrtion of potssium ions in the photoreeptor lyer, due to light sorption in the photoreeptors, eliits hnges in the trns-memrne potentil of the Müller ells nd is expressed s the slow P-III omponent of the ERG. Choroidl lyer Fst P-III Slow P-III

32 The origin of the mjor ERG wves. The -wve T k e - H o m e M e s s g e The ERG -wve is the leding prt of Grnit's P-III omponent. Numerous studies indite tht the fst P-III omponent of the ERG reflets light-indued tivity of the photoreeptors. The slow omponent of the P-III nnot e identified in regulr ERG response due to the lrge mplitude positive P-I wve. Choroidl lyer

33 The origin of the mjor ERG wves. The -wve The inner retin is involved in the prodution of the -wve. Choroidl lyer

34 The origin of the mjor ERG wves. The -wve The inner retin is involved in the prodution of the -wve. Choroidl lyer 1961 Bloking synpti trnsmission from the reeptors to seond order retinl neurons y sturting the post-synpti reeptors with L-sprtte or L-glutmte, elimintes the ERG -wve nd isoltes the P-III omponent The -wve is lso eliminted when the lood flow through the entrl retinl rtery is loked either intentionlly in lortory nimls (Noell, 1954; Brown nd Wtne, 1962), or in humn ptients (Nilsson, 1971).

35 The origin of the mjor ERG wves The -wve Fer reported tht sink for the -wve ws in the distl prt of the retin, most proly in the outer plexiform lyer, while the soure ws distriuted proximlly nd distlly to the sink. The only retinl elements tht hve sptil distriution similr to the -wve soures nd sinks re the Müller glil ells Choroidl lyer The most effe re potssium (Miller, 1973) Intrellulr reording from Müller ells in the Neturus retin supports Fer's ides (Miller nd Dowling, 1970) ve is lso eliminted when the through the entrl retinl rtery either intentionlly in lortory oell, 1954; Brown nd Wtne, 1962), or tients (Nilsson, 1971) Fer (1969) ws the first to lulte the extrellulr urrents tht underlie the ERG -wve of the rit eye. 1971

36 The origin of the mjor ERG wves. The -wve The slow depolrizing response of Müller ells to light stimulus followed temporl pttern, similr to tht of the ERG -wve reorded from the sme retin. Furthermore, the mplitude-stimulus intensity reltionship ws similr for the Müller ell photoresponses nd the ERG -wve. Bsed on these oservtions, Miller nd Dowling (1970) suggested tht depolriztion of the Müller ell memrne in the distl retin resulted in extrellulr urrents tht were expressed s the -wve. A hnge in the extrellulr onentrtion of ions tht permete through the Müller ells' memrne my use hnge in memrne potentil Choroidl lyer The ide tht the -wve results from memrne potentil of the Müller e 1973 indued hnges of extrellu The most effetive onentrtion, underlies the sis for re potssium ions Hypothesis". (Miller, 1973) Intrellulr reording from Müller ells in the Neturus retin supports Fer's ides (Miller nd Dowling, 1970)

37 The origin of the mjor ERG wves. The -wve Sine first proposed, this ide hs een tested y mny investigtors using intrellulr reordings from Müller ells, mesurements of extrellulr onentrtions of potssium nd reording the ERG t different retinl depths. Studies were done in mudpuppy (Krwoski nd Proenz, 1980; Krwoski et l., 1985), frog (Newmn, 1980; Newmn nd Odette, 1984; Newmn, 1985), fish (Kline et l., 1978, 1985), rit (Dik et l., 1985; Krwoski nd Xu, 1999), t (Brown nd Wiesel, 1961, 1961; Arden nd Brown, 1965) nd monkey (Heynen nd vn Norren, 1985, 1985). These nd other studies reported light-indued inrese in extrellulr potssium in the outer nd inner plexiform lyers. This inrese ws thought most likely due to lekge from depolrizing retinl neurons. Choroidl lyer The most effetive re potssium ions (Miller, 1973) The ide tht the -wve results from hnges in the memrne potentil of the Müller ells due to lightindued hnges of extrellulr potssium onentrtion, underlies the sis for the "Müller-ell Hypothesis". More evidene onerning the ERG -wve ws gine gonists nd ntgonists reeptors.

38 The origin of the mjor ERG wves. The -wve It ws ssumed tht the origin of potssium inreses in the outer plexiform lyer ws ipolr ells, most speifilly ON-enter ipolr ells tht were depolrized y light (Dik nd Miller, 1985). In the inner plexiform lyer, the inrese in extrellulr potssium resulted from light-indued tivity of mrine nd gnglion ells (Krwoski nd Proenz, 1977; Dik nd Miller, 1985). The hnge in potssium lters the memrne potentil of Müller ells, generting eletril urrents in these two regions of the Müller ell, nd exiting through its distl nd proximl ends (Ripps nd Witkovsky, 1985). Depth reordings of extrellulr onentrtion of potssium nd of lol field potentils lerly show redution of potssium ions in the photoreeptor lyer nd n inrese in the outer nd inner plexiform lyers. Choroidl lyer The most effetive re potssium ions (Miller, 1973) The ide tht the -wve results from hnges in the memrne potentil of the Müller ells due to lightindued hnges of extrellulr potssium onentrtion, underlies the sis for the "Müller-ell Hypothesis". More evidene onerning the ERG -wve ws gine gonists nd ntgonists reeptors.

39 The origin of the mjor ERG wves. The -wve 1973 It ws ssumed tht the origin of potssium inreses in the outer plexiform lyer ws ipolr ells, most speifilly ON-enter ipolr ells tht were depolrized y light (Dik nd Miller, 1985). In the inner plexiform lyer, the inrese in extrellulr potssium resulted from light-indued tivity of mrine nd gnglion ells (Krwoski nd Proenz, 1977; Dik nd Miller, 1985). The hnge in potssium lters the memrne potentil of Müller ells, generting eletril urrents in these two regions of the Müller ell, nd exiting through its distl nd proximl ends (Ripps nd Witkovsky, 1985). Depth reordings of extrellulr onentrtion of potssium nd of lol field potentils lerly show redution of potssium ions in the photoreeptor lyer nd n inrese in the outer nd inner plexiform lyers. Current soure-density nlysis of these dt led to the pthwys of the extrellulr urrents to underlie the genertion of the ERG -wve. The two sinks ( nd ) reflet the inrese in extrellulr potssium ions due to light-indued eletril tivity. The The most effetive re potssium ions (Miller, 1973) vitreous serves s lrge urrent soure due to the high potssium ondutne of the endfeet of the Muller ells (Newmn, 1985) The ide tht the -wve results from hnges in the memrne potentil of the Müller ells due to lightindued hnges of extrellulr potssium onentrtion, underlies the sis for the "Müller-ell Hypothesis" Choroidl lyer More evidene onerning the ERG -wve ws gine gonists nd ntgonists reeptors.

40 The origin of the mjor ERG wves. The -wve Exposing the verterte retin to 2-mino-4-phosphonoutyri id (APB), speifi gonist of glutmte metotropi reeptors, elimintes the ERG -wve (Gurevih nd Slughter, 1993) Sine APB-sensitive metotropi glutmte reeptors re found only in ON-enter ipolr ells (Slughter nd Miller, 1981), this finding onstitutes ler indition of the involvement of these ipolr ells in the genertion of the -wve. Further support me from experiments in whih the effets of 6,7-dinitroquinoxline-2,3- dione (DNQX) upon the ERG were tested. Using tetrodotowin (TTX) to lok tio third-order retinl neurons (mrine nd nd speifi ntgonists to GABA nd gl it ws onluded tht third-order neuron the mplitude nd kinetis of the ERG Hre, 2000). In primtes, Sieving nd outhors (1994 This drug is speifi ntgonist to AMPA/KA type glutmte 1994 reeptors, nd propose enhnes tht the the -wve of the photop -wve, proly y removing urrent soures tht oppose those forming the -wve. ERG response re minly ontriuted the ON-enter ipolr ells ut re oppose y OFF-enter ipolr ells Choroidl lyer ve results from hnges in the of the Müller ells due to lightof extrellulr potssium lies the sis for the "Müller-ell 1993 More evidene onerning the soure of the ERG -wve ws gined with speifi gonists nd ntgonists to glutmte reeptors. 1999

41 The origin of the mjor ERG wves. The -wve This led to "push-pull model' of Using these tetrodotowin ell types (Sieving (TTX) et l., to 1994). lok tion potentils in More reent detiled sink-soure third-order nlyses (Krwoski retinl neurons nd Xu, 1999), (mrine phrmologil nd gnglion dissetion ells), of the ERG (Green nd Kpoust-Bruneu, 1999) nd nd speifi experiments ntgonists with to GABA mglur6 nd knokout glyine reeptors, mie (Msu et l. it ws onluded tht third-order neurons ontriuted to 1995) points diretly to the ON-enter ipolr ells s generting the ERG -wve without the mplitude nd kinetis of the ERG -wve (Dong nd the Müller ells. Hre, 2000). This oservtion (nd others using rium) opposes the Müller ells hypothesis for the ERG -wve nd thus, supports the ON-enter ipolr ell 2000hypothesis. Choroidl lyer In primtes, Sieving nd outhors (1994) propose tht the -wve of the photopi ERG response re minly ontriuted y the ON-enter ipolr ells ut re opposed y OFF-enter ipolr ells. 1999

42 The origin of the mjor ERG wves. The -wve Another study on the retin-eyeup preprtion of the tiger slmnder, shows tht drugs disrupts the tivity of third order neurons nd uses enhnement of the -wve (Awtrmni et l., 2001). The -wve is lso found to e ffeted y drugs tht modulte GABAC-type reeptors inditing tht negtive feedk from mrine ells onto ipolr ells n shpe the photoresponses of the ipolr ells nd thus, the mplitude nd kinetis of the ERG -wve (Dong nd Hre, 2002). GABAA nd GABAC pthwys re lso found to ffet the ERG -wve of the rt retin (Kpoust-Bruneu, 2000). Biuulline, the ntgonist for GABAA-type reeptors ugments the -wve, while, 3- minopropylphosphono id (3-APMPA), the ntgonist for GABAC-type reeptors redues it. Using tetrodotowin (TTX) to lok tion potentils in third-order retinl neurons (mrine nd gnglion ells), nd speifi ntgonists to GABA nd glyine reeptors, it ws onluded tht third-order neurons ontriuted to the mplitude nd kinetis of the ERG -wve (Dong nd Hre, 2000) Choroidl lyer

43 The origin of the mjor ERG wves. The -wve T k e - H o m e M e s s g e ON-enter ipolr ells generte the ERG -wve without the Müller ells. Third-order neurons (mrine nd gnglion ells) ontriute to the mplitude nd kinetis of the ERG -wve. The -wve is found to e ffeted y drugs tht modulte GABAC-type reeptors Choroidl lyer