Ocular pigmentation in white and Siamese cats

Transcription

1 Ocular pigmentatin in white and Siamese cats L. N. Thibs,. R. Levick, and R. Mrstyn Ocular pigmentatin in white cats with blue and. yellw eyes and in Siamese cats was examined phthalmscpically and histlgically. Yellw-eyed, white cats had. entirely nrmal cular pigmentatin. Blue eyes f white cats had. nrmal pigmentatin f the iridial and. retinal pigment epithelia but n strmal pigmentatin f the iris r chrid. This deficit is apparently due t the absence f strmal pigment cells, certainly in the iris. As a general rule, the blue eye f white cats had n tapetum. Siamese cats had reduced pigmentatin f the iridial and retinal pigment epithelia and n strmal pigmentatin f the iris r chrid. The lack f pigmentatin is apparently due t the inability f strmal pigment cells t prduce pigment, certainly in the iris. e cnclude that the abnrmality f visual pathways previusly described, in the Siamese cat is nt due simply t a deficiency f pigment in cells f neural crest rigin. Key wrds: cular pigments, white cats, Siamese cats, iris pigment, chrid pigment v3iamese and white cats are tw breeds which have a deficiency f cat pigmentatin and which can als have reduced cular pigmentatin. The cmparative details f this hyppigmentatin are f interest because the Siamese cat suffers frm an abnrmal visual pathway 1 " 3 yet the white cat des nt. 4 Albin individuals f ther mammalian species have pathway abnrmalities similar t thse in the Siamese cat, and the suggestin has been made that the cause might be specifically related t the amunt f pigment in the retinal epithelium. 5 6 ' Frm the Department f Physilgy, Jhn Curtin Schl f Medical Research, Australian Natinal University, Canberra, Australia. L. N. Thibs was supprted by a Pstdctral Fellwship f the U. S. Public Health Service. R. Mrstyn was a Vacatin Schlar f the Australian Natinal University. Submitted fr publicatin Dec. 27, Reprint requests: Dr.. R. Levick, Department f Physilgy, Jhn Curtin Schl f Medical Research, Australian Natinal University, P.O. Bx 334, Canberra City, A.C.T. 2601, Australia. This reprt describes the extent f cular pigmentatin in white cats as cmpared with Siamese and nrmally pigmented cats. Several f the animals used in these experiments were als subjects in neurphysilgical investigatins f the visual pathways which are described elsewhere. 4 Methds Ophthalmscpic bservatins f six adult white cats (A thrugh F) f undetermined genetic cnstitutin were made after each animal was prepared fr neurphysilgical recrdings. The pupil was dilated with atrpine drps (1%), and a zer-pwer cntact lens was fitted. Additinal bservatins were made n six white, five Siamese, and ne slid black cat (cats G thrugh S). Clr phtgraphs f the fundus and iris were taken with a Zeiss fundus camera and Kdaclr 400 film. Upn cmpletin f neurphysilgical experiments, a dse f abut 30 mg f pentbarbitne per kilgram f bdy weight was administered intravenusly, and the eyes were enucleated. Each eye was then hemisected at the pars plana, the vitreus and lens were discarded, and the remainder was fixed in 10% neutral buffered frmal saline /80/ $01.20/ Assc. fr Res. in Vis. and Ophthal., Inc. 475

2 476 Thibs, Levick, and Mrstyn Invest. Ophthalml, Vis. Set. May 1980 Fig. 1. Fr legend see facing page.

3 Vlume 19 Number 5 Ocular pigmentatin in cat All T get satisfactry iris preparatins, animals G thrugh R, which were nt part f neurphysilgical experiments, were given 2 drps f 0.5% physstigmine t cntract the pupil. A lethal dse f pentbarbitne was administered, and the eyes were enucleated and fixed as described abve. Befre the histlgical preparatin was begun, fundus tissue was sandwiched between slices f fixed cat liver t minimize detachment f the retina frm the chrid. Tissues were embedded in paraffin, and 5 /u,m sectins were prepared with hematxylin and esin stain. In sme preparatins melanin pigment was bleached by treatment with 0.1% ptassium permanganate fllwed by 1% xalic acid. Phtmicrgraphs were taken with a Zeiss phtmicrscpe. Results Ophthalmscpic and micrdissectin bservatins. A summary f the grss appearance f the irides and fundi f the 18 subjects is given in Table I. Iris. Clr phtgraphs f the living cat iris are given in Fig. 1, A, fr a yellw-eyed white cat and in Fig. 1, C, fr a blue-eyed white cat. Dissectin f the eyes f white cats revealed the psterir surfaces f the irides t be as darkly pigmented as in the rdinary pigmented cat. Side-by-side cmparisn under transilluminatin shwed that the yellw and blue irides f white cats were each as paque as the yellw iris f a black cat. The blue iris f a seal-pint Siamese cat is shwn in Fig. 1, E. The psterir surface f the Siamese iris was nt as heavily pigmented as in the rdinary pigmented cat, appearing a dark chclate brwn in the seal pint and a lighter brwn in the lilac pint. Under transilluminatin the iris had a translucent t diaphanus appearance, quite different in sideby-side cmparisn with irides f white cats. Fundus. The dminant feature f an rdinary pigmented cat's fundus is the yellwgreen tapetum which is surrunded by very dark pigmentatin. Althugh the precise size and shape f the tapetum varies smewhat frm cat t cat, 7 it is pssible t predict the lcatin f the tapetum with acceptable reliability. e shall refer t this fiducial regin where ne expects t find a tapetal reflectin as the tapetal zne. The statements which fllw are based upn cmplete phthalmscpic and micrdissectin surveys f the entire fundi supprted by selected fundus phtgraphs. The fundi f yellw-eyed white cats had the same appearance as thse f rdinary pigmented cats. A yellw-green reflectin frm the tapetal zne and the retinal bld vessels within this regin were clearly visible phthalmscpically (e.g., upper part f Fig. 1, B). The shape and size f the tapetum was within the nrmal range. 7 The nntapetal zne appeared dark brwn (e.g., lwer part f Fig. 1, B) due t the presence f pigment in bth the retinal epithelium and chrid as bserved by micrdissectin. Hwever, in eight f 12 eyes there were hrizntally elngated patches f inferir fundus abut 5 t 10 mm wide and 2 t 4 mm high where chridal pigment was cmpletely missing. Apart frm these patches, the chrid was equally heavily pigmented inside and utside the tapetal zne. The fundus f the usual blue-eyed white Fig. 1. Iris and fundus f the living cat eye. Shwn are yellw-eyed white cat iris (A) and fundus (B), blue-eyed white cat iris (C) and fundus (D), and seal-pint Siamese iris (E) and fundus (F) (left eye f animals Q, R, and S, respectively). The darkly pigmented pupillary ruff f the epithelium, lcated at the pupil margin, is mre evident in A and C than in E. Nte the translucent quality f the Siamese iris. Fundus phtgraphs all shw the inferir brder f the tapetal zne with the retinal bld vessels exiting frm the ptic nerve head in the upper left f the picture. Each field subtends abut 30 f visual angle and each is centered apprximately 15 belw and 7 nasal t the center f the area centralis, s as t shw parts f bth tapetal and nntapetal znes. B has the appearance f the rdinary pigmented cat's fundus. D lacks bth tapetum and chridal pigment, thereby revealing chridal bld vessels. Clumps f retinal epithelial pigment are evident at the bttm f D. Because f the absence f a reflecting tapetum, the expsure fr this phtgraph had t be increased substantially relative t B and F. F has a tapetum, dilute epithelial pigment, but n chridal pigment; thus the chridal vessels are visible belw the tapetal zne.

4 478 Thibs, Levick, and Mrstyn Invest. Ophthalml. Vis. Sci. May 1980 Table I. Summary f macrscpic appearance f cular pigmentatin Cat identificatin /breed Iris clr Iris epithelium Chrid Tapetum Retina epithelium utside tapetal zne Eye R L R L R L R L R G Bl A F Y Y Y H Q w B Of O D E L C I w- p w R J SS Y Y By Y By B B B B B B B B Y Bv B B B B B B M SS N SS B s SS B K LS B O G O O O O O O O O = white cat; Bl = black cat; SS = Seal-pint Siamese cat; LS = Lilac-pint Siamese cat. Letter O nt used fr identificatin f cat. Y = yellw appearance; B = blue appearance; By = blue with yellw sectr. Key: Pigment (r tapetum) present; O pigment diluted; O pigment (r tapetum) absent. '"Absence f pigment in a prtin f inferir fundus. tquadrantic sectr f pigment in tempral midperiphery. cat was strikingly different frm that f the rdinary pigmented cat. 8-9 There was n bright yellw reflectin frm the tapetal zne, nr was there any chridal pigmentatin. Hence in viv the tapetal zne had the appearance f a jungle f red bld vessels (e.g., upper part f Fig. 1, D). Micrdissectin f the fixed eyecup shwed cmplete lack f chridal pigmentatin. There were the fllwing exceptins. In three eyes a predminantly blue iris was partly yellw; in tw f these eyes the fundus had bth tapetum and chridal pigment. In all the blue-eyed white cats the pigment f the retinal epithelium was present utside the tapetal zne but nt within, just as in nrmal eyes. Pigmentatin is shwn in the lwer part f Fig. 1, D, partly bscuring the chridal bld vessels. The Siamese fundus in viv shwed a slightly desaturated tapetal reflectin (e.g., upper half f Fig. 1, F) and utside the tapetal zne appeared reddish brwn 10 (e.g., lwer part f Fig. 1, F). Micrdissectin shwed that there was n chridal pigmentatin. Visibility f the tapetum was reduced in the fixed eye cup, prbably because the absence f chridal pigment led t increased amunts f scattered light. The distributin f pigment in the retinal epithelium was the same as fr the white cats described abve. Hwever, side-by-side cmparisn between fundi f the Siamese and blue-eyed white cats, neither f which had chridal pigment, shwed that the white cat's epithelial pigment was significantly darker. Even at the brder f the tapetal zne where the epithelial pigmentatin just began, it was bserved that the pigment clumps in the white cat were darker than pigment in any part f the Siamese retinal epithelium. This dilutin f epithelial pigment was quite definite in the seal-pint Siamese and even mre bvius in the lilac-pint. Histlgical bservatins Yellw iris. A crss-sectinal view f the yellw iris taken frm a black cat is shwn in Fig. 2, A, and frm a yellw-eyed white cat in Fig. 2, B. The pigmentatin f the white cat's iris is the same as fr the black cat's iris: bth have heavily pigmented epithelial cells plus light brwn pigment cells f the strma. The strmal pigment is in the frm f lng thin filaments similar t that fund in rhesus mnkey iris strmal cells 11 knwn t be true melancytes. 12 ' 13 Thus it is likely that the cat's strmal pigment cells are als melancytes. A magnified view f individual strmal pigment cells is given in Fig. 3, A. Perikaryal

5 Vlume 19 Number 5 Ocular pigmentatin in cat 479 B 100 y Fig. 2. Crss-sectins f irides frm black (A), yellw-eyed white (B), blue-eyed white (C), and Siamese (D) cats (animals G, H, I, and K, respectively). Specimens riented with psterir (epithelial) surface t left, anterir (strmal) t right. Magnificatin bar (100 ju,m) is cmmn t all. Pigment cells (PC) and pupillary ruff(r) are labeled in A nly.

6 480 Thibs, Levick, and Mrstyn Invest. Ophthalml. Vis. Set. May J980 A B Fig. 3. Tangential sectins f irides f yellw-eyed white (B), blue-eyed white (C) and Siamese (D) cats (same animals as in Fig. 2). Presumed pigment cell nuclei (PN) indicated by arrws. Magnificatin bar (100 /Am) in B applies t B t D nly. A, High-magnificatin view f three pigment cells fund at varius lcatins f the iridial strma in yellw-eyed white cat f B.

7 Vlume 19 Number 5 Ocular pigmentatin in cat 481 Fig. 4. Fundus crss-sectins in nntapetal regin apprximately 5 t 7 mm belw the area centralis in black (A), yellw-eyed white (B), blue-eyed white (C) and Siamese (D) cats (animals G, H, I, and J, respectively). Structures indicated are phtreceptrs (R), retinal epithelium (E), chridfcj, sclerafsj, and bld vessel (B). Magnificatin bar (100 JLUTI) is cmmn t all. Separatin f layers is artefactual.

8 482 Thibs, Levick, and Mrstyn Invest, Ophthalml. Vis. Set. May 1980 Fig. 5. Fundus crss-sectins in tapetal regin apprximately 3 mm abve the area centralis. Animals used and key t structures indicated are as in Fig. 4. Tapetum (T) is als shwn. Magnificatin bar (100 fxm) is cmmn t all.

9 Vlume 19 Number 5 Ocular pigmentatin in cat 483 shape varies frm nearly circular t lng and slender. A cnstant feature f these cells is the large, darkly stained, val nucleus. The mean f the minimum and maximum nuclear diameters determined fr 20 cells ranged frm 4.75 t 7.25 /am and averaged 5.5 /xm. Such nuclei were fund nly within the pigmented cells f the strma. Strmal pigment cells tended t be cncentrated n the anterir surface f the iris. A tangential sectin made parallel t the iris surface therefre revealed a large number f pigment cells fr bth black and yellw-eyed white cats (Fig. 3, B). The greatest density f pigment cells was fund at invaginatins and at the margin f these sectins, which was the mst anterir prtin f the tissue. Blue iris. Crss-sectins f the blue-eyed white cat's iris shwed a nrmal, heavily pigmented epithelium (Fig. 2, C). N pigmented cells were fund in tangential sectins f iris (Fig. 3, C). e ruled ut the pssibility that such cells were present but unpigmented, as suggested by Lauber, 14 because nne f the strmal nuclei had the quantitative characteristics described abve. Pigmentatin in the Siamese blue iris was distinctly different frm that f the blue-eyed white cat. The layer f pigment within the epithelium was thinner, and the granules were less densely packed, particularly in the lilac-pint animal. Cnsequently individual pigment granules culd be bserved, and the nrmal pupillary ruff was hardly evident (Fig. 2, D). The strma was nt pigmented, but cntrary t the situatin in the blue-eyed white cat, the pigment cells were evidently present. This cnclusin is based n the tangential sectin f Fig. 3, D, which shws many large val nuclei having the expected quantitative characteristics. Fundus f the yellw eye. The cmparisn f pigmentatin in different eyes is mst straightfrward if ne avids the margin f the tapetal zne where the thickness f epithelial pigment varies. Accrdingly, the data presented belw fr the tapetal zne are frm the regin abut 3 mm abve the area centralis and fr the nntapetal zne is frm the regin abut 7 mm belw the area centralis. Pigmentatin f chrid and retinal epithelium in the nntapetal zne fr a black cat is shwn in Fig. 4, A, and the yellw-eyed white cat in Fig. 4, B. Epithelial pigment thickness was in the range f 10 t 20 /Am in these cats. A heavy infiltratin f pigment bscured the nuclei f the chridal cells, but bleaching revealed the nuclei t be f variable size and shape with n unambiguus identifying characteristics. The thickness f the chrid was due mainly t bld vessels rather than the thin pigment cells. ithin the tapetal zne f the black (Fig. 5, A) and yellw-eyed white (Fig. 5, B) cat fundus the retinal epithelium was devid f pigment, and the large, rughly circular nuclei f this single-cell layer were evident. The tapetal cells were easily recgnized by their large nuclei, elngated perikaryn, regular array, and particular clratin. The chrid was equally heavily pigmented in the tapetal and nntapetal znes. Fundus f the blue eye. Outside the tapetal zne the blue-eyed white cat's fundus (Fig. 4, C) had heavily pigmented retinal epithelial cells. Abve the area centralis within the tapetal zne the retinal epithelium was unpigmented (Fig. 5, C) as in the rdinary pigmented cat, but tapetal cells were absent entirely. There was n chridal pigmentatin. Because n unique features f chridal pigment cells had been fund in the rdinary pigmented cat, we were unable t determine whether in the blue-eyed white cat the pigment cells were present and unpigmented r cmpletely absent. The Siamese cat had a thinner than nrmal layer f pigment in the retinal epithelium in the nntapetal zne (Fig. 4, D). Frm the edge f the tape turn t the ra terminalis, the maximum thickness f the epithelial pigment layer in the seal-pint retina was 5 (xm and in the lilac-pint 3 fxm, cnsiderably less than in the rdinary pigmented cat. ithin the tapetal zne there was n epithelial pigment and the tapetal cells appeared nrmal. Chridal pigmentatin was cmpletely absent thrughut the fundus, but it culd nt be

10 484 Thibs, Levick, and Mrstyn Invest. Ophthalml. Vis. Sci. May 1980 determined whether the pigment cells were absent altgether r present but devid f pigment. Discussin The results f this study are best summarized in relatin t the pstulated embrylgical surce f the varius types f cular pigment cells. This is nt knwn specifically fr the cat, but the fllwing descriptin is cmmn t ther mammals, 15 ' 16 birds, 17 and amphibia. 18 Pigment cells f the iris and chridal strmata are derived frm cells which migrate frm the neural crest. The tapetal cells f the cat are likely t be mdified chridal pigment cells 19 and hence als f neural crest rigin. On the ther hand, the pigment epithelia f the retina and iris are prducts f the embrynic eye cup. Our results shw that the yellw-eyed white cat has nrmal cular pigmentatin but the blue-eyed white cat lacks pigment in the iridial and chridal strmata. The basis f the deficit in the blue eye appears t be the absence f the pigment cell itself. Presumably the neural crest cells either failed t migrate t the cular tissue r failed t differentiate and survive as uveal pigment cells. The Siamese cat is als deficient in cular pigment but in quite a different way. First, there is a relative diminutin f pigmentatin f the iridial and retinal epithelia. Secnd, the cmmn lack f pigmentatin in iridial and chridal strmata is assciated with the presence f unpigmented pigment cells, certainly in the iris and pssibly als in the chrid. In summary, the blue-eyed white cat lacks a particular cell type, whereas the Siamese is defective in pigment prductin. There were exceptins t the abve generalizatins. Three f 12 blue irides f white cats had yellw sectrs, and in ne f these eyes there was a patch f chridal pigmentatin. In eight f 12 yellw eyes f white cats the chridal pigmentatin was incmplete. This hetergeneity might indicate the presence f piebald sptting in the eye. It has lng been suspected 20 that a blue eye wuld appear if a cat carrying the gene fr dminant white als carried the gene pattern fr piebald sptting f the eye. hite spts wuld be undetectable in the cmpletely white hair and pink skin caused by dminant white, but the edges f a spt might be revealed by the cular pigment. Tapetum lucidum. The results btained frm blue-eyed white cats have shwn that the usual deletin f pigment frm the retinal epithelium within the tapetal zne is nt under direct tapetal cntrl, since in these cats the tapetal cells were absent but the distributin f retinal epithelial pigment was nrmal. Bernstein and Pease 19 have suggested that tapetal cells are mdified chridal melancytes. The Siamese has heretfre been in apparent cntradictin t this hypthesis, since chridal pigment is missing yet the animal has a nrmal tapetum. The incnsistency is reslved if the present results n iris tissue are generalized t include chrid. e may suppse that unpigmented chridal pigment cells are likely t be present in the Siamese cat and therefre the derivative tapetal cells wuld be present as well. If this be true, it wuld imply that functinal tapetal rds, which are the basis f light reflectin phenmena, 21 are nt dependent upn melanin prductin. Genetics. The all-white cat f the white cat is inherited as a dminant character 8 ' 20 " 22 and therefre cannt be the result f the actin f an allele at the albin lcus. 23 There has been nly ne reprt f an albin cat, 24 but it is cmmnly believed that the Siamese breed represents an imperfect frm f albinism, as first suggested many years ag. 25 ' 26 The evidence fr this view is that (1) Siamese is a recessive characteristic 2 ' resulting in hyppigmentatin and (2) the pattern f thermlabile cat pigmentatin in the Siamese cat resembles that in the Himalayan rabbit, 28 ' 29 the gene f which is knwn t be allelmrphic with the albin gene. 27 The cause f the lack f pigment in albin animals and sme albin humans appear t be a failure f individual melancytes t prduce pigment because f default f the enzyme tyrsinase. l6-30> 31 A piebald white spt,

11 Vlume 19 Number 5 Ocular pigmentatin in cat 485 n the ther hand, results frm the failure f neural crest-derived pigment cells t survive. 16 ' 32 Thus ne finds amelantic melancytes, r "clear cells," in the skin and hair bulbs f albin individuals but nt in piebald individuals M Our bservatin f clear cells in the iris strma f the Siamese but nt in the white cat prvides further experimental supprt fr the idea that Siamese is a member f the albin series whereas dminant white is related t piebaldism, and is cnsistent with the idea first prpsed by right 34 that Siamese and white cats are tw breeds deficient in pigment as a result f entirely distinct genetic mechanisms. Optic nerve decussatin. e have shwn elsewhere 4 that the decussatin f ptic nerve fibers in white cats is indistinguishable frm nrmal. Cupled with the present anatmical results, this means that nrmal develpment f the visual pathways may prceed withut neural crest-derived pigment cells and rules ut the pssibility that the Siamese neural abnrmality is simply due t the lack f pigment in cells f neural crest rigin. The hypthesis that neural develpment depends upn ptic cup pigmentatin 5-6 may still be cnsistent with the results f this paper. One argument against this view, hwever, is that in cats with nrmal visual pathways the retinal epithelium is unpigmented in the tapetal zne. Examples frm the literature 7-35 indicate that this unpigmented regin is frm V3 t V2 the area f the retina and may include % f the retinal ganglin cells. 36 If the adult pattern f epithelial pigment distributin is als present in the develping embry (an assumptin we have verified in fetuses as small as 11 mm crwn-rump length), then it is difficult t see hw the presence f pigmentatin utside the tapetal zne culd cntrl the decussatin f axns arising frm ganglin cells within the tapetal zne. If the pigment hypthesis becmes untenable, then it may be that the embrynic cntrl f ptic nerve decussatin is related t sme mre fundamental abnrmality in Siamese, such as a defective enzyme tyrsinase, and that reduced pigmentatin is merely ne particular reflectin f that defect. 6 e are grateful t Miss. Hughes wh prepared the histlgical slides. Mrs. E. van de Pl rendered valuable technical assistance. e appreciated the technical supprt prvided by Messrs. L. M. Davies, R. M. Tupper, and P. C. Kent and members f the Phtgraphic Service. The fundus camera used in this study was generusly prvided by the Lins Club f Canberra. REFERENCES 1. Guillery R: An abnrmal retin-geniculate prjectin in Siamese cats. Brain Res 14:739, Kalil R, Jhavery S, and Richards R: Anmalus retinal pathways in the Siamese cat: an inadequate substrate fr nrmal bincular visin. Science 174: 302, Hubel D and iesel TN: Aberrant visual prjectins in the Siamese cat. J Physil 218:33, Levick R, Thibs LN, and Mrstyn R: Retinal ganglin cells and ptic decussatin in white cats. (Submitted fr publicatin.) 5. Sandersn KJ, Guillery R, and Shackelfrd RM: Cngenitally abnrmal visual pathways in mink {hiustela visin) with reduced retinal pigment. J Cmp Neurl 154:225, LaVail JR, Nixn RA, and Sidman RL: Genetic cntrl f retinal ganglin cell prjectins. J Cmp Neurl 182:399, Bishp PO, Kzak, and Vakkur GJ: Sme quantitative aspects f the cats eye: axis and plane f reference, visual field c-rdinates and ptics. J Physil 163:466, Bergsma DR and Brwn KS: hite fur, blue eyes, and deafness in the dmestic cat. J Hered 62:171, Tjebbes K: Crsses with Siamese cats. J Genet 14:355, Jhnsn GL: Ophthalmscpic studies n the eyes f mammals. Phils Trans R Sc Lndn Ser B 254:207, Tusimis AJ: Pigment cells f the mammalian iris. Ann NY Acad Sci 100:477, Hu F and Mntagna : The develpment f pigment cells in the eyes f Rhesus mnkeys. Am J Anat 132:119, End H and Hu F: Pigment cell develpment in Rhesus mnkey eyes: an electrn micrscpic and histchemical study. Dev Bil 32:69, Lauber H: Anatmische Untersuchungen iiber Heterchrmie bei tauben, unvllkmmen albintischen Katzen. Ophthalmlgica 16:326, Rawles ME: Origin f pigment cells frm the neural crest in the muse embry. Physil Zl 20:248, Billingham RE and Silvers K: The melancytes f mammals. Q Rev Bil 35:1, 1960.

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